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Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients

Last updated on October 16, 2019

FOR MORE INFORMATION
Study Location
Massachusetts General Hospital
Boston, Massachusetts, 02114 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Metastatic Pancreatic Ductal Adenocarcinoma
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. Histologically or cytologically proven diagnosis of metastatic ductal adenocarcinoma
of the pancreas.

2. All patients must provide a baseline tumor sample at registration. If an archival
sample is not available, patients must have a metastatic biopsy collected at the
screening visit.

3. Patient must have received no previous radiotherapy, surgery, chemotherapy or
investigational therapy for the treatment of metastatic disease.

4. Measurable disease as per RECIST v. 1.1.

5. Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI
CTCAE.

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

7. Age ≥18 years.

8. Adequate Bone Marrow, Renal and liver Functions.

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

1. Patients with known symptomatic brain metastases requiring steroids.

2. Prior therapy with modulators of monocyte or TAM function.

3. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4
weeks of registering for the current study and/or during study participation.

4. Diagnosis of any second malignancy within the last 3 years, except for adequately
treated basal cell carcinoma, or squamous cell skin carcinoma or in situ cervical
carcinoma.

5. Known hypersensitivity to nab-paclitaxel or to gemcitabine or to any of the
excipients.

6. Any one of the following currently or in the previous 6 months: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic
congestive heart failure, cerebrovascular accident, transient ischemic attack;
symptomatic pulmonary embolism; congenital long QT syndrome, torsades de points,
arrhythmias (including sustained ventricular tachyarrhythmia and ventricular
fibrillation), right bundle branch block and left anterior hemiblock (bifascicular
block), ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of
any grade, or QTc interval >470 msec at screening.

7. Concurrent administration of herbal preparations.

8. Use of oral anticoagulants. Use of subcutaneous anti coagulation is allowed.
Concurrent use of potent or moderate inhibitors or inducers of CYP3A4 and/or CYP2C8.

9. Active and clinically significant bacterial, fungal or viral infection including
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or
acquired immunodeficiency syndrome (AIDS) related illness.

10. History of interstitial lung disease, or slowly progressive dyspnea and unproductive
cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
hypersensitivity pneumonitis or multiple allergies.

11. Other severe 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.

12. Pregnant female patients; breastfeeding female patients; males patients with partners
currently pregnant, male patients able to father children and female patients of
childbearing potential who are unwilling or unable to use two (2) highly effective
methods of contraception as outlined in this protocol for the duration of the study
and for 28 days after last dose of PF-04136309, and for 6 months after last dose of
nab-paclitaxel, gemcitabine, or both.

13. Patients who are investigational site staff members directly involved in the conduct
of the trial and their family members, site staff members otherwise supervised by the
Investigator, or patients who are Pfizer employees directly involved in the conduct of
the trial.

NCT02732938
Pfizer
Terminated
Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients

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Descriptive Information
Brief Title  ICMJE Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients
Official Title  ICMJE PHASE 1B/2 STUDY OF PF-04136309 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
Brief SummaryThe purpose of this Phase 1b/2 study is to evaluate the safety and tolerability of PF-04136309 in combination with nab-paclitaxel and gemcitabine, characterize the dose-limiting toxicities (DLTs) and overall safety profile of escalated doses of PF-04136309 and the associated schedule, determine the maximum tolerated dose (MTD), and to assess the enhancement of efficacy of PF-04136309 in combination with nab-paclitaxel and gemcitabine versus nab-paclitaxel + gemcitabine + placebo in terms of Progression Free Survival.
Detailed Description

The study has 2 parts:

Phase 1b (dose-finding cohorts) will be open label as patients will receive ascending doses of PF-04136309 in combination with nab-paclitaxel + gemcitabine. The observation period for dose-limiting toxicities (DLTs) will be from Day 1 to Day 28. Pharmacokinetic (PK) and pharmacodynamic (PD) properties of PF-04136309 will also be assessed. The criteria for dose escalation will be based on a modified toxicity probability interval (mTPI) method. After evaluating the safety and other results (eg, PK) from patients enrolled in the dose escalation cohorts, a dose level will be selected to be further evaluated as the Recommended Phase 2 Dose (RP2D). A minimum of 6 patients, up to 12 patients, will be treated at this dose level to establish it as the RP2D. To further evaluate safety and pharmacodynamics, the number of patients enrolled during this part of the study (Phase 1b) may be N up to 20. The study will stop if all PF-04136309 doses explored appear to be overly toxic.

Phase 2 randomized double blinded placebo control. Approximately 92 patients will be randomized 1:1 to receive the RP2D of PF-04136309 in combination with nab-paclitaxel + gemcitabine (ARM A; n=46) versus nab-paclitaxel + gemcitabine + placebo (ARM B; n=46). The primary objective will be the enhancement of efficacy in terms of PFS.

Patients will be treated as long as they are clinically benefiting from investigational product without unacceptable toxicity, objective disease progression, or withdrawal of consent.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Ductal Adenocarcinoma
Intervention  ICMJE
  • Drug: PF-04136309
    PF-04136309 oral dosing
  • Drug: Nab-paclitaxel
    Nab-paclitaxel IV dosing
    Other Name: Abraxane
  • Drug: Gemcitabine
    Gemcitabine IV dosing
    Other Name: Gemzar
Study Arms  ICMJE Experimental: PF-04136309 + Nab-p + Gem

PF-04136309 oral dosing

Nab-paclitaxel IV dosing Gemcitabine IV dosing

Interventions:
  • Drug: PF-04136309
  • Drug: Nab-paclitaxel
  • Drug: Gemcitabine
Publications *Noel M, O'Reilly EM, Wolpin BM, Ryan DP, Bullock AJ, Britten CD, Linehan DC, Belt BA, Gamelin EC, Ganguly B, Yin D, Joh T, Jacobs IA, Taylor CT, Lowery MA. Phase 1b study of a small molecule antagonist of human chemokine (C-C motif) receptor 2 (PF-04136309) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic ductal adenocarcinoma. Invest New Drugs. 2019 Jul 12. doi: 10.1007/s10637-019-00830-3. [Epub ahead of print]


*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: June 19, 2018)
22
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2016)
112
Actual Study Completion Date  ICMJE October 10, 2017
Actual Primary Completion DateSeptember 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Histologically or cytologically proven diagnosis of metastatic ductal adenocarcinoma of the pancreas.
  2. All patients must provide a baseline tumor sample at registration. If an archival sample is not available, patients must have a metastatic biopsy collected at the screening visit.
  3. Patient must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
  4. Measurable disease as per RECIST v. 1.1.
  5. Resolved acute effects of any prior therapy to baseline severity or Grade ?1 NCI CTCAE.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  7. Age ?18 years.
  8. Adequate Bone Marrow, Renal and liver Functions.

Exclusion Criteria

  1. Patients with known symptomatic brain metastases requiring steroids.
  2. Prior therapy with modulators of monocyte or TAM function.
  3. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks of registering for the current study and/or during study participation.
  4. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma or in situ cervical carcinoma.
  5. Known hypersensitivity to nab-paclitaxel or to gemcitabine or to any of the excipients.
  6. Any one of the following currently or in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack; symptomatic pulmonary embolism; congenital long QT syndrome, torsades de points, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of any grade, or QTc interval >470 msec at screening.
  7. Concurrent administration of herbal preparations.
  8. Use of oral anticoagulants. Use of subcutaneous anti coagulation is allowed. Concurrent use of potent or moderate inhibitors or inducers of CYP3A4 and/or CYP2C8.
  9. Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
  10. History of interstitial lung disease, or slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
  11. Other severe 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.
  12. Pregnant female patients; breastfeeding female patients; males patients with partners currently pregnant, male patients able to father children and female patients of childbearing potential who are unwilling or unable to use two (2) highly effective methods of contraception as outlined in this protocol for the duration of the study and for 28 days after last dose of PF-04136309, and for 6 months after last dose of nab-paclitaxel, gemcitabine, or both.
  13. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02732938
Other Study ID Numbers  ICMJE A9421018
2015-003767-11 ( EudraCT Number )
Has Data Monitoring CommitteeNo
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:Yes
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/da....
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/da...
Responsible PartyPfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS AccountPfizer
Verification DateDecember 2018

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

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