Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors

NCT03065062

Last updated date
Study Location
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Contact
617-632-4942

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Lung Cancer Squamous Cell, Solid Tumors, Head & Neck Cancer, Pancreatic Cancer
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

- For Part I, participants must have histologically confirmed malignancy that is metastatic or unresectable and resistant to standard therapy or for which no standard therapy is available. For Part II, participants must have histologically confirmed advanced squamous cell lung cancer, advanced pancreatic cancer, advanced head & neck cancer (specifically non-oropharynx squamous cell carcinoma or HPV-negative oropharynx squamous cell carcinoma), or any tumor with suspected PI3K-pathway dependence (either by mutation or by known biologic rationale, such as endometrial cancer. PI3K dependence includes the presence of a PIK3CA-mutant hotspot mutation, PIK3CA copy number gain, or PTEN loss in the archival or fresh tumor tissue specimen identified in a CLIA-certified laboratory. All genetic findings must be reviewed by the study PI, prior to study entry.)

- For Part I, participants are required to have only evaluable disease (disease that is visible on imaging studies but does not meet RECIST criteria for measurable disease). For Part II, participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.

- Participants are permitted to have any number of prior therapies prior to enrollment

- Age ≥ 18 years. .

- ECOG performance status ≤ 2

- Participants must have normal organ and marrow function as defined below:

- Absolute neutrophil count ≥ 1,500/mcL

- Hemoglobin ≥9.0 gm/dL

- Platelets ≥ 100,000/mcL

- Total bilirubin within normal institutional limits

- AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal (≤ 5.0 X institutional upper limit of normal permitted if hepatic metastases present)

- Creatinine within 1.5x the ULN institutional limits

- Fasting glucose ≤ 126 mg/dL (7.0 mmol/L)

- HbA1c ≤ 7.0%

- The effects of palbociclib and Gedatolisib (PF-05212384) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 90 days after discontinuation.

- Ability to understand and the willingness to sign a written informed consent document.

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


- Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from acute effects of any prior therapy to baseline or Grade ≤1 except for
Alopecia or AEs not constituting a safety risk in the opinion of the investigator.


- Participants may not be receiving any other study agents concurrently with the study
drugs.


- Participants with symptomatic brain metastases that require active treatment are
excluded.


- Current use or anticipated need for food or medications that are known strong CYP3A4
inhibitors/inducers, including their administration within 7-days prior to the first
Gedatolisib (PF-05212384) or palbocilib dose and during study treatment.


- QTc > 480 msec; history of QT syndrome, Brugada syndrome or known history of QTc
prolongation, or Torsade de Pointes.


- Patients with a history of diabetes.


- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.


- Pregnant women are excluded from this study because the study agents have the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk of adverse events in nursing infants secondary to treatment of the
mother with the study agents, breastfeeding should be discontinued if the mother is
treated.


- Individuals with a history of other malignancy are ineligible except for the following
circumstances. Individuals with a history of previous malignancies are eligible if
they have been disease-free for at least 2 years and are deemed by the investigator to
be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer
in situ, and basal cell or squamous cell carcinoma of the skin.


- 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.


- Concurrent use or anticipated need for medications that are mainly metabolized by
UGT1A9 including their administration within 7-days prior to the first dose of study
drug.


- Current use or anticipated need for food or medications that are metabolized by
CYP2D6, and of narrow therapeutic index including their administration within 10-days
prior to the first Gedatolisib (PF-05212384) dose and during study treatment.


- Concurrent use of herbal preparations including saw palmetto.


- Current use of drugs known to prolong QT interval.


- Concurrent use of proton pump inhibitors (including, but not limited to,
dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
with palbociclib is prohibited.

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Lung Cancer Squamous Cell, Solid Tumors, Head & Neck Cancer, Pancreatic CancerStudy of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors
NCT03065062
  1. Boston, Massachusetts
  2. Boston, Massachusetts
  3. Boston, Massachusetts
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors
Official Title  ICMJE Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors
Brief Summary This research study is studying a combination of drugs as a possible treatment for cancer that might have a specific change in the phosphatidylinositol-3 phosphate (PI3K) pathway.
Detailed Description

This research study is an open-label Phase I clinical trial, which tests the safety of an investigational drug or combination of investigational drugs and also tries to define the appropriate dose of the investigational drug(s) to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Palbociclib for the participant specific disease but it has been approved for other uses. The FDA has not approved Gedatolisib alone or in combination with Palbociclb as a treatment option for the participant's disease.

In this research study the investigators hope to determine if treatment with Palbociclib and Gedatolisib will be tolerated and will help to shrink or stop the growth of the participant's cancer. Palbociclib is an oral drug which has been shown to stop the cell cycle, which is the way a cell initiates growth. Gedatolisib is thought to work by controlling a series of events directing cell growth and survival. Gedatolisib may work to stop or slow activity within tumor cells. By putting these two drugs together the investigators hope that it will have a greater effect on cancer growth than either drug alone.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lung Cancer Squamous Cell
  • Solid Tumors
  • Head & Neck Cancer
  • Pancreatic Cancer
Intervention  ICMJE
  • Drug: Palbociclib
    Palbociclib will be administered orally once daily, 3 weeks out of every 4 in each cycle. The initial dose for part 1 of the study will be 100 mg daily. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. No pre-medications for palbociclib are required. It should be administered with food.
    Other Names:
    • IBRANCE
    • PD-0332991
  • Drug: Gedatolisib
    Gedatolisib will be administered once weekly on the first day for each of the four weeks during the 4-week cycle. The initial dose for part 1 of the study will be 110 mg. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. No pre-medications for gedatolisib are required.
    Other Name: PF-05212384
Study Arms  ICMJE Experimental: Combination Of Palbociclib and Gedatolisib
  • Palbociclib will be administered orally once daily on Days 1-21 for each of the 4-week cycles at a pre-determined dose.
  • Gedatolisib will be administered intravenously once weekly on the first day for each of the four weeks during the 4-week cycles at a pre-determined dose.
Interventions:
  • Drug: Palbociclib
  • Drug: Gedatolisib
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: February 22, 2017)
96
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • For Part I, participants must have histologically confirmed malignancy that is metastatic or unresectable and resistant to standard therapy or for which no standard therapy is available. For Part II, participants must have histologically confirmed advanced squamous cell lung cancer, advanced pancreatic cancer, advanced head & neck cancer (specifically non-oropharynx squamous cell carcinoma or HPV-negative oropharynx squamous cell carcinoma), or any tumor with suspected PI3K-pathway dependence (either by mutation or by known biologic rationale, such as endometrial cancer. PI3K dependence includes the presence of a PIK3CA-mutant hotspot mutation, PIK3CA copy number gain, or PTEN loss in the archival or fresh tumor tissue specimen identified in a CLIA-certified laboratory. All genetic findings must be reviewed by the study PI, prior to study entry.)
  • For Part I, participants are required to have only evaluable disease (disease that is visible on imaging studies but does not meet RECIST criteria for measurable disease). For Part II, participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
  • Participants are permitted to have any number of prior therapies prior to enrollment
  • Age ? 18 years. .
  • ECOG performance status ? 2
  • Participants must have normal organ and marrow function as defined below:

    • Absolute neutrophil count ? 1,500/mcL
    • Hemoglobin ?9.0 gm/dL
    • Platelets ? 100,000/mcL
    • Total bilirubin within normal institutional limits
    • AST (SGOT)/ALT (SGPT) ? 2.5 X institutional upper limit of normal (? 5.0 X institutional upper limit of normal permitted if hepatic metastases present)
    • Creatinine within 1.5x the ULN institutional limits
    • Fasting glucose ? 126 mg/dL (7.0 mmol/L)
    • HbA1c ? 7.0%
  • The effects of palbociclib and Gedatolisib (PF-05212384) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 90 days after discontinuation.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute effects of any prior therapy to baseline or Grade ?1 except for Alopecia or AEs not constituting a safety risk in the opinion of the investigator.
  • Participants may not be receiving any other study agents concurrently with the study drugs.
  • Participants with symptomatic brain metastases that require active treatment are excluded.
  • Current use or anticipated need for food or medications that are known strong CYP3A4 inhibitors/inducers, including their administration within 7-days prior to the first Gedatolisib (PF-05212384) or palbocilib dose and during study treatment.
  • QTc > 480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
  • Patients with a history of diabetes.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because the study agents have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated.
  • Individuals with a history of other malignancy are ineligible except for the following circumstances. Individuals with a history of previous malignancies are eligible if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
  • 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.
  • Concurrent use or anticipated need for medications that are mainly metabolized by UGT1A9 including their administration within 7-days prior to the first dose of study drug.
  • Current use or anticipated need for food or medications that are metabolized by CYP2D6, and of narrow therapeutic index including their administration within 10-days prior to the first Gedatolisib (PF-05212384) dose and during study treatment.
  • Concurrent use of herbal preparations including saw palmetto.
  • Current use of drugs known to prolong QT interval.
  • Concurrent use of proton pump inhibitors (including, but not limited to, dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) with palbociclib is prohibited.
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: Geoffrey Shapiro, MD617-632-4942[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03065062
Other Study ID Numbers  ICMJE 16-499
Has Data Monitoring Committee Yes
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
Responsible Party Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Geoffrey Shapiro, MDDana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date July 2020

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