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 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: 16-499
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

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.

Conditions

Head & Neck Cancer; Pancreatic Cancer; Lung Cancer Squamous Cell; Solid Tumors

Keywords

Lung Cancer Squamous Cell; Head & Neck Cancer; Neoplasms; Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose and Recommended Phase 2 Dose

  The dose-escalation schedule will use the mTPI design to discover the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of palbociclib and gedatolisib.

  2 years

• Incidence of Treatment-Emergent Adverse Events

  Number of participants with treatment-related adverse events as assessed by version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE).

  2 years

Secondary Outcomes (9)

• Progression Free Survival Rate at 4 months

  4 months

• Target engagement of palbociclib and gedatolisib in paired tumor biopsies

  2 years

• Pharmacokinetic parameter (maximum concentration [Cmax]) of gedatolisib in the absence or presence of palbociclib

  At 0.5, 1, 2, 4, 6, 8, 10, 24, 72, 120 and 168 hours after dosing (lead-in dose 7 days prior to cycle 1 day 1, and cycle 1 day 15)

• Pharmacokinetic parameter (area under the curve [AUC]) of gedatolisib in the absence or presence of palbociclib

  At 0.5, 1, 2, 4, 6, 8, 10, 24, 72, 120 and 168 hours after dosing (lead-in dose 7 days prior to cycle 1 day 1, and cycle 1 day 15)

• Pharmacokinetic parameter (half-life [t1/2]) of gedatolisib in the absence or presence of palbociclib

  At 0.5, 1, 2, 4, 6, 8, 10, 24, 72, 120 and 168 hours after dosing (lead-in dose 7 days prior to cycle 1 day 1, and cycle 1 day 15)

Study Arms (1)

Combination Of Palbociclib and Gedatolisib

EXPERIMENTAL

* 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.

Drug: Palbociclib; Drug: Gedatolisib

Interventions

Palbociclib DRUG

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.

Also known as: IBRANCE, PD-0332991

Combination Of Palbociclib and Gedatolisib

Gedatolisib DRUG

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.

Also known as: PF-05212384

Combination Of Palbociclib and Gedatolisib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Pancreatic Neoplasms; Neoplasms; Endometrial Neoplasms

Interventions

palbociclib; gedatolisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Geoffrey Shapiro, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2017
• First Posted: February 27, 2017
• Study Start: February 28, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)