PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors

NCT03685591

Last updated date
Study Location
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Breast Neoplasms, Prostate Neoplasms, Squamous Cell Neoplasms, Melanoma, Mesothelioma, Pancreatic Neoplasms, Colorectal Neoplasms, Renal Cell Carcinoma, Liver Neoplasms
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. For Part 1A: Histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients are intolerant to standard treatment, resistant to standard therapy or for which no standard therapy is available for the following tumor types:

Breast cancer; Prostate cancer (mCRPC testosterone less than 50 ng/dL); Squamous cell cancer of the head and neck; Melanoma; Mesothelioma; Pancreatic cancer; Colorectal cancer; Renal cell carcinoma; Hepatocellular cancer.

2. For Part 1B, Part 2A, and Part 2B:

- Histologically or cytologically confirmed prostate adenocarcinoma metastatic disease.

- Effective castration with serum testosterone levels 0.5 ng/mL (1.7 nmol/L).

- Having received 3 or more cycles of prior docetaxel therapy (before or after abiraterone).

- Having PD while receiving abiraterone acetate within 12 months of abiraterone treatment initiation.

- Progressive disease (PD) by:

1. Progression in measurable disease per RECIST 1.1 criteria. Patient with measurable disease must have at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) (CT scan thickness no greater than 5 mm) or magnetic resonance imaging (MRI). Lymph nodes should be greater than or equal to 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion, and bone lesions will be considered non-measurable disease, or

2. Appearance of 2 or more new bone lesions (PCWG2). They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results, or

3. Rising PSA defined (PCWG2) as at least 2 consecutive rises in PSA to be documented over a reference value (measure 1) taken at least 1 week apart. • Prior abiraterone acetate must be stopped at least 2 weeks before study treatment.

3. Patients must have recently obtained archival tumor tissue available for submission to the sponsor (except for Part 2A - monotherapy dose expansion). Patients enrolled in Part 1 and Part 2 should have access to their archival formalin-fixed paraffin-embedded material, collected within 6 months of screening, containing tumor that is of diagnostic quality and representative of their diagnosed malignancy or whenever possible, consent to undergo a biopsy during screening. The sponsor should be contacted if obtaining a new biopsy is not medically feasible for approval to enroll, prior to initiating screening activities.

4. Patients entering the study in the subgroup(s) requiring mandatory pre- and on treatment tumor biopsies in Part 2A and 2B must have a tumor amenable to biopsy and consent to these planned biopsy procedures. The sponsor should be contacted if obtaining a pre-treatment and on treatment biopsies is not medically feasible for approval to enroll, prior to initiating screening activities.

5. Age 18 years or older

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

7. Adequate bone marrow function (see Appendix 3), including:

- Absolute Neutrophil Count (ANC) greater than or equal to 1,500/mm3;

- Platelets greater than or equal to 100,000/mm3;

- Hemoglobin greater than or equal to 9 g/dL.

8. Adequate renal function, including serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or estimated creatinine clearance greater than or equal to 60 mL/min as calculated using the method standard for the institution. In equivocal cases, a 24 hour urine collection test can be used to estimate the creatinine clearance more accurately. In Part 2: Serum creatinine of less than or equal to 3.0 x upper limit of normal.

9. Adequate liver function, including:

- Total serum bilirubin less than or equal to 0.5 x ULN unless the patient has documented Gilbert syndrome;

- Aspartate and alanine aminotransferase (AST and ALT) less than or equal to 2.5 x ULN less than or equal to 5.0 x ULN if there is liver involvement by the tumor;

- Alkaline phosphatase less than or equal 2.5 x ULN less than or equal to 5 x ULN in case of bone metastasis).

10. Serum phosphate within normal range (if abnormal, must be nonclinically significant per the Investigator and approval for patient inclusion after agreement from sponsor.

11. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for alopecia and those listed in the specific exclusion criteria.

12. For Part 1A monotherapy dose escalation: serum pregnancy test (for females of childbearing potential) negative at screening.

13. For Part 1A monotherapy dose escalation: female patients of nonchildbearing potential must meet at least 1 of the following criteria:

- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and must have a serum follicle stimulating hormone level confirming the postmenopausal state;

- Have undergone a documented hysterectomy and/or bilateral oophorectomy;

- Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.

14. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.

15. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


Patients with any of the characteristics/conditions listed below will not be included in
the study:


Any labs may be repeated for confirmation. Only the lab result requiring confirmation must
be repeated, not the entire panel.


1. For Parts 1B, 2A, and 2B:


- Prior chemotherapy other than docetaxel for prostate cancer, except estramustine,
adjuvant/neoadjuvant treatment completed more than 3 years ago;


- Less than 28 days elapsed from prior treatment with chemotherapy, immunotherapy,
radiotherapy, or surgery to the time of study enrollment.


2. Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal
disease as indicated by baseline brain MRI (or CT with contrast if MRI is medically
contraindicated), clinical symptoms, cerebral edema, and/or progressive growth. If
contrast is medically contraindicated, a non-contrast CT scan may be performed.


3. Patients with a history of CNS metastases or cord compression.


4. Liver metastases at baseline as evidenced by CT scan or MRI that may be at risk for
bleeding, such as those that are greater than 1 cm,


5. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of
life threatening complications in the short term (including patients with massive
uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and
over 50% liver involvement). Note: Patients with indwelling catheter for drainage, or
requirement for drainage no more frequently than monthly will be allowed.


6. Any other active malignancy within 3 years prior to study entry, except for adequately
treated basal cell or squamous cell skin cancer, or carcinoma in situ.


7. Patients with a history of clinically significant tumor bleeding (except for bleeding
in a post-operative setting), coagulopathy or arterio-venous malformations (AVM) or
aneurysms in the CNS, liver, lung or other major organ of the body. Patients with
known Osler-Weber-Rendu disease, Hemophilia A, Hemophilia B (Christmas Disease), Von
Willibrand's Disease, Factor 13 deficiency and Factor 7 deficiency, antibodies to
Factors 8 and 7, history of other bleeding diatheses and abnormal INR values.


8. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation
that in the opinion of the investigator is likely to bleed.


9. Major surgery within 4 weeks prior to first dose.


10. Prior organ transplantation including heart and allogeneic stem cell transplantation.


11. Radiation therapy within 4 weeks prior to study entry. Note: Patients who have
received radiotherapy must have recovered from any reversible side effects, such as
nausea and vomiting.


12. Last anti cancer therapy including investigational drug(s) within 28 days (or 5
half-lives, whichever is shorter) prior to study entry excluding hormonal therapy.


13. Active and clinically significant bacterial, fungal, or viral infection, including
known hepatitis B virus (HBV), known hepatitis C virus (HCV), known human
immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related
illness. In equivocal cases, with positive serology, those patients with a negative
viral load are potentially eligible provided the other entry criteria are met. Note:
Inclusion of patients with well controlled HIV, HBV or HCV can be discussed with
sponsor on a case by case basis.


• COVID-19/SARS-CoV2: Refer to Appendix 8 for further information.


14. Any of the following in the previous 6 months: myocardial infarction, congenital long
QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular
tachyarrhythmia and ventricular fibrillation), right bundle branch block and left
anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery
bypass graft, symptomatic congestive heart failure (New York Heart Association class
III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic
pulmonary embolism; deep venous thrombosis (DVT); arterial occlusive disease; ongoing
cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE Grade 2 or higher ,
atrial fibrillation of any grade that is uncontrolled, or QTcF interval greater than
470 msec at screening. Note: There is an exception where a cardiac rhythm
device/pacemaker is fitted and results in QTcF greater than 470 msec.


15. Anticoagulation therapy with heparin, low molecular weight heparin, vitamin K
antagonists, anti-platelet agents, or factor Xa inhibitors throughout the study and
for at least 28 days post the last dose of study treatment. (If anticoagulation
therapy is medically indicated on trial, patients should stop treatment with
PF-06952229. For those requiring temporary anticoagulant therapy, resumption of
PF-06952229 treatment may be permitted after discussion with the Sponsor. In any other
case, study treatment should be permanently discontinued, and the patient should enter
the follow-up portion of the trial.)


16. Moderate or severe heart valve function defect including moderate or severe valve
stenosis or regurgitation.


17. Evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the
major vessels.


18. Grade 3 or higher cardiac troponin I at baseline.


19. Left ventricular ejection fraction (LVEF) of less than or equal to 50% or significant
valvular regurgitation.


20. Hypertension that cannot be controlled by medications (greater than 150/90 mmHg
despite optimal medical therapy) or requiring more than 2 medications for adequate
control.


21. Clinically significant non healing or healing wounds.


22. For patients entering the combination with enzalutamide arm, history of seizures other
than isolated febrile seizure in childhood.


23. Has a history of a cerebrovascular accident or transient ischemic attack less than 6
months ago.


24. Known or suspected hypersensitivity to active ingredient/excipients of PF 06952229 or
enzalutamide.


25. Other acute or chronic medical or psychiatric condition, including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this
study.


26. Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees, including their family members, directly involved
in the conduct of the study.


27. For Part 1A Monotherapy Dose Escalation: Pregnant female patients; breastfeeding
female patients; fertile male patients and female patients of childbearing potential
who are unwilling or unable to use 2 highly effective methods of contraception as
outlined in this protocol for the duration of the study and for at least 28 days after
the last dose of investigational product.


28. For Part 1B Combination Dose Escalation, Part 2A Monotherapy Expansion, and Part 2B
Combination Dose Expansion: fertile male patients and female partners of childbearing
potential who are unwilling or unable to use 2 highly effective methods of
contraception as outlined in this protocol for the duration of the study and for at
least 28 days after the last dose for monotherapy (Part 2A) or for at least 3 months
after the last dose for combination therapy (Part 1B and Part 2B).


29. Inability to consume or absorb study drug, including but not limited to:


• Active inflammatory gastrointestinal (GI) disease, known diverticular disease or
previous gastric resection or lap band surgery. Impairment of gastro intestinal
function or GI disease that may significantly alter the absorption of PF 06952229,
such as history of GI surgery with may result in intestinal blind loops and patients
with clinically significant gastroparesis, short bowel syndrome, unresolved nausea,
vomiting, active inflammatory bowel disease or diarrhea of CTCAE Grade greater than 1.


30. Current use or anticipated need for food or drugs that are known strong and moderate
CYP3A4/5 inhibitors, including their administration within 10 days or 5 half lives of
the CYP3A4/5 inhibitor, whichever is longer, prior to first dose of investigational
product.


31. Current use or anticipated need for drugs that are known strong and moderate CYP3A4/5
inducers, including their administration within 10 days or 5 half lives of the
CYP3A4/5 inducer, whichever is longer, prior to the first dose of investigational
product (See Section 5.7).


32. Have initiated bisphosphonates or approved receptor activator of nuclear factor kappa
B ligand (RANK L) targeted agents (for example, denosumab) less than 14 days prior to
study entry, unless there is agreement with the medical monitor.


33. Active, known suspect suspected autoimmune diseases including inflammatory bowel
disease (including ulcerative colitis and Crohn's disease), rheumatoid arthritis,
systemic progressive sclerosis, systemic lupus erythematosus (SLE), autoimmune
vasculitis (eg, Wegener's Granulomatosis), CNS or motor neuropathy considered to be of
autoimmune origin (eg, Gullian Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis).

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Breast Neoplasms, Prostate Neoplasms, Squamous Cell Neoplasms, Melanoma, Mesothelioma, Pancreatic Neoplasms, Colorectal Neoplasms, Renal Cell Carcinoma, Liver NeoplasmsPF-06952229 Treatment in Adult Patients With Advanced Solid Tumors
NCT03685591
  1. Boston, Massachusetts
  2. Boston, Massachusetts
  3. Boston, Massachusetts
  4. Chelsea, Massachusetts
  5. Danvers, Massachusetts
  6. Waltham, Massachusetts
  7. Scottsdale, Arizona
  8. Santa Monica, California
  9. Oklahoma City, Oklahoma
  10. Oklahoma City, Oklahoma
  11. Nashville, Tennessee
  12. Nashville, Tennessee
  13. Houston, Texas
  14. San Antonio, Texas
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors
Official Title  ICMJE A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF 06952229 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
Brief Summary A Phase 1 dose escalation and expansion study evaluating safety, tolerability and pharmacokinetics of PF-06952229 in adult patients with advanced solid tumors.
Detailed Description

This is a Phase 1, open label, multi center, multiple dose, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06952229 in previously treated patients with advanced or metastatic cancers that may have high TGFbeta signatures and EMT expression.

The study includes Parts 1A and 1B, which are dose-escalation for monotherapy and combination therapy with enzalutamide, respectively, and Parts 2A and 2B, which are dose expansion for monotherapy and combination therapy with enzalutamide, respectively.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Neoplasms
  • Prostate Neoplasms
  • Neoplasms, Squamous Cell
  • Melanoma
  • Mesothelioma
  • Pancreatic Neoplasms
  • Colorectal Neoplasms
  • Carcinoma, Renal Cell
  • Liver Neoplasms
Intervention  ICMJE
  • Drug: PF-06952229
    Oral 7 days on / 7 days off - 28 day cycles (Part 1)
  • Drug: Enzalutamide
    Prostate Cancer (Part 2). 160mg, capsules, orally, daily
Study Arms  ICMJE
  • Experimental: Dose Level 1 (Part 1A)
    PF-06952229 at 20mg twice daily (BID)
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 2 (Part 1A)
    PF-06952229 at 40 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 3 (Part 1A)
    PF-06952229 at 80 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 4 (Part 1A)
    PF-06952229 at 150 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 5 (Part 1A)
    PF-06952229 at 250 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 6 (Part 1A)
    PF-06952229 at 375 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 7 (Part 1A)
    PF-06952229 at 500 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 8 (Part 1A)
    PF-06952229 at 625 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Dose Level 9 (Part 1A)
    PF-06952229 at 750 mg BID
    Intervention: Drug: PF-06952229
  • Experimental: Prostate Cancer Dose Level 1 (Part 1B)
    PF-06952229 at 375 mg BID in combination with enzalutamide
    Interventions:
    • Drug: PF-06952229
    • Drug: Enzalutamide
  • Experimental: Prostate Cancer Dose Level 2 (Part 1B)
    PF-06952229 at 500 mg BID in combination with enzalutamide
    Interventions:
    • Drug: PF-06952229
    • Drug: Enzalutamide
  • Experimental: Prostate Cancer Dose Level 3 (Part 1B)
    PF-06952229 at 625 mg BID in combination with enzalutamide
    Interventions:
    • Drug: PF-06952229
    • Drug: Enzalutamide
  • Experimental: Prostate Cancer Dose Level 4 (Part 1B)
    PF-06952229 at 750 mg BID in combination with enzalutamide
    Interventions:
    • Drug: PF-06952229
    • Drug: Enzalutamide
  • Experimental: Prostate Cancer (Part 2A)
    PF-06952229 at recommended Phase 2 Dose BID
    Intervention: Drug: PF-06952229
  • Experimental: Prostate Cancer (Part 2B)
    PF-06952229 at recommended phase 2 dose BID in combination with enzalutamide
    Interventions:
    • Drug: PF-06952229
    • Drug: Enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 21, 2020)
90
Original Estimated Enrollment  ICMJE
 (submitted: September 25, 2018)
100
Estimated Study Completion Date  ICMJE January 17, 2025
Estimated Primary Completion Date March 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. For Part 1A: Histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients are intolerant to standard treatment, resistant to standard therapy or for which no standard therapy is available for the following tumor types:

    Breast cancer; Prostate cancer (mCRPC testosterone less than 50 ng/dL); Squamous cell cancer of the head and neck; Melanoma; Mesothelioma; Pancreatic cancer; Colorectal cancer; Renal cell carcinoma; Hepatocellular cancer.

  2. For Part 1B, Part 2A, and Part 2B:

    • Histologically or cytologically confirmed prostate adenocarcinoma metastatic disease.
    • Effective castration with serum testosterone levels 0.5 ng/mL (1.7 nmol/L).
    • Having received 3 or more cycles of prior docetaxel therapy (before or after abiraterone).
    • Having PD while receiving abiraterone acetate within 12 months of abiraterone treatment initiation.
    • Progressive disease (PD) by:

      1. Progression in measurable disease per RECIST 1.1 criteria. Patient with measurable disease must have at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) (CT scan thickness no greater than 5 mm) or magnetic resonance imaging (MRI). Lymph nodes should be greater than or equal to 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion, and bone lesions will be considered non-measurable disease, or
      2. Appearance of 2 or more new bone lesions (PCWG2). They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results, or
      3. Rising PSA defined (PCWG2) as at least 2 consecutive rises in PSA to be documented over a reference value (measure 1) taken at least 1 week apart. ? Prior abiraterone acetate must be stopped at least 2 weeks before study treatment.
  3. Patients must have recently obtained archival tumor tissue available for submission to the sponsor (except for Part 2A - monotherapy dose expansion). Patients enrolled in Part 1 and Part 2 should have access to their archival formalin-fixed paraffin-embedded material, collected within 6 months of screening, containing tumor that is of diagnostic quality and representative of their diagnosed malignancy or whenever possible, consent to undergo a biopsy during screening. The sponsor should be contacted if obtaining a new biopsy is not medically feasible for approval to enroll, prior to initiating screening activities.
  4. Patients entering the study in the subgroup(s) requiring mandatory pre- and on treatment tumor biopsies in Part 2A and 2B must have a tumor amenable to biopsy and consent to these planned biopsy procedures. The sponsor should be contacted if obtaining a pre-treatment and on treatment biopsies is not medically feasible for approval to enroll, prior to initiating screening activities.
  5. Age 18 years or older
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  7. Adequate bone marrow function (see Appendix 3), including:

    • Absolute Neutrophil Count (ANC) greater than or equal to 1,500/mm3;
    • Platelets greater than or equal to 100,000/mm3;
    • Hemoglobin greater than or equal to 9 g/dL.
  8. Adequate renal function, including serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or estimated creatinine clearance greater than or equal to 60 mL/min as calculated using the method standard for the institution. In equivocal cases, a 24 hour urine collection test can be used to estimate the creatinine clearance more accurately. In Part 2: Serum creatinine of less than or equal to 3.0 x upper limit of normal.
  9. Adequate liver function, including:

    • Total serum bilirubin less than or equal to 0.5 x ULN unless the patient has documented Gilbert syndrome;
    • Aspartate and alanine aminotransferase (AST and ALT) less than or equal to 2.5 x ULN less than or equal to 5.0 x ULN if there is liver involvement by the tumor;
    • Alkaline phosphatase less than or equal 2.5 x ULN less than or equal to 5 x ULN in case of bone metastasis).
  10. Serum phosphate within normal range (if abnormal, must be nonclinically significant per the Investigator and approval for patient inclusion after agreement from sponsor.
  11. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for alopecia and those listed in the specific exclusion criteria.
  12. For Part 1A monotherapy dose escalation: serum pregnancy test (for females of childbearing potential) negative at screening.
  13. For Part 1A monotherapy dose escalation: female patients of nonchildbearing potential must meet at least 1 of the following criteria:

    • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and must have a serum follicle stimulating hormone level confirming the postmenopausal state;
    • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    • Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.
  14. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
  15. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Exclusion Criteria

Patients with any of the characteristics/conditions listed below will not be included in the study:

Any labs may be repeated for confirmation. Only the lab result requiring confirmation must be repeated, not the entire panel.

  1. For Parts 1B, 2A, and 2B:

    • Prior chemotherapy other than docetaxel for prostate cancer, except estramustine, adjuvant/neoadjuvant treatment completed more than 3 years ago;
    • Less than 28 days elapsed from prior treatment with chemotherapy, immunotherapy, radiotherapy, or surgery to the time of study enrollment.
  2. Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by baseline brain MRI (or CT with contrast if MRI is medically contraindicated), clinical symptoms, cerebral edema, and/or progressive growth. If contrast is medically contraindicated, a non-contrast CT scan may be performed.
  3. Patients with a history of CNS metastases or cord compression.
  4. Liver metastases at baseline as evidenced by CT scan or MRI that may be at risk for bleeding, such as those that are greater than 1 cm,
  5. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement). Note: Patients with indwelling catheter for drainage, or requirement for drainage no more frequently than monthly will be allowed.
  6. Any other active malignancy within 3 years prior to study entry, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
  7. Patients with a history of clinically significant tumor bleeding (except for bleeding in a post-operative setting), coagulopathy or arterio-venous malformations (AVM) or aneurysms in the CNS, liver, lung or other major organ of the body. Patients with known Osler-Weber-Rendu disease, Hemophilia A, Hemophilia B (Christmas Disease), Von Willibrand's Disease, Factor 13 deficiency and Factor 7 deficiency, antibodies to Factors 8 and 7, history of other bleeding diatheses and abnormal INR values.
  8. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the investigator is likely to bleed.
  9. Major surgery within 4 weeks prior to first dose.
  10. Prior organ transplantation including heart and allogeneic stem cell transplantation.
  11. Radiation therapy within 4 weeks prior to study entry. Note: Patients who have received radiotherapy must have recovered from any reversible side effects, such as nausea and vomiting.
  12. Last anti cancer therapy including investigational drug(s) within 28 days (or 5 half-lives, whichever is shorter) prior to study entry excluding hormonal therapy.
  13. Active and clinically significant bacterial, fungal, or viral infection, including known hepatitis B virus (HBV), known hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. In equivocal cases, with positive serology, those patients with a negative viral load are potentially eligible provided the other entry criteria are met. Note: Inclusion of patients with well controlled HIV, HBV or HCV can be discussed with sponsor on a case by case basis.

    ? COVID-19/SARS-CoV2: Refer to Appendix 8 for further information.

  14. Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep venous thrombosis (DVT); arterial occlusive disease; ongoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE Grade 2 or higher , atrial fibrillation of any grade that is uncontrolled, or QTcF interval greater than 470 msec at screening. Note: There is an exception where a cardiac rhythm device/pacemaker is fitted and results in QTcF greater than 470 msec.
  15. Anticoagulation therapy with heparin, low molecular weight heparin, vitamin K antagonists, anti-platelet agents, or factor Xa inhibitors throughout the study and for at least 28 days post the last dose of study treatment. (If anticoagulation therapy is medically indicated on trial, patients should stop treatment with PF-06952229. For those requiring temporary anticoagulant therapy, resumption of PF-06952229 treatment may be permitted after discussion with the Sponsor. In any other case, study treatment should be permanently discontinued, and the patient should enter the follow-up portion of the trial.)
  16. Moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation.
  17. Evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the major vessels.
  18. Grade 3 or higher cardiac troponin I at baseline.
  19. Left ventricular ejection fraction (LVEF) of less than or equal to 50% or significant valvular regurgitation.
  20. Hypertension that cannot be controlled by medications (greater than 150/90 mmHg despite optimal medical therapy) or requiring more than 2 medications for adequate control.
  21. Clinically significant non healing or healing wounds.
  22. For patients entering the combination with enzalutamide arm, history of seizures other than isolated febrile seizure in childhood.
  23. Has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
  24. Known or suspected hypersensitivity to active ingredient/excipients of PF 06952229 or enzalutamide.
  25. Other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  26. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
  27. For Part 1A Monotherapy Dose Escalation: Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
  28. For Part 1B Combination Dose Escalation, Part 2A Monotherapy Expansion, and Part 2B Combination Dose Expansion: fertile male patients and female partners of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose for monotherapy (Part 2A) or for at least 3 months after the last dose for combination therapy (Part 1B and Part 2B).
  29. Inability to consume or absorb study drug, including but not limited to:

    ? Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery. Impairment of gastro intestinal function or GI disease that may significantly alter the absorption of PF 06952229, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE Grade greater than 1.

  30. Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer, prior to first dose of investigational product.
  31. Current use or anticipated need for drugs that are known strong and moderate CYP3A4/5 inducers, including their administration within 10 days or 5 half lives of the CYP3A4/5 inducer, whichever is longer, prior to the first dose of investigational product (See Section 5.7).
  32. Have initiated bisphosphonates or approved receptor activator of nuclear factor kappa B ligand (RANK L) targeted agents (for example, denosumab) less than 14 days prior to study entry, unless there is agreement with the medical monitor.
  33. Active, known suspect suspected autoimmune diseases including inflammatory bowel disease (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus (SLE), autoimmune vasculitis (eg, Wegener's Granulomatosis), CNS or motor neuropathy considered to be of autoimmune origin (eg, Gullian Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis).
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03685591
Other Study ID Numbers  ICMJE C3881001
C3881001 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP