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Palbociclib and Gedatolisib in Treating Patients with Advanced Solid Tumors or Lung, Pancreatic, or Head and Neck Cancer

Trial Status: Active

This phase I trial studies the side effects and best dose of palbociclib and gedatolisib and how well they work in treating patients with solid tumors or lung, pancreatic, or head and neck cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Palbociclib and gedatolisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • 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
  • PART II: participants must have one of the following, histologically confirmed * Advanced squamous cell lung cancer * KRAS-mutant lung cancer * Advanced pancreatic cancer * Advanced head & neck cancer (specifically non-oropharynx squamous cell carcinoma or human papillomavirus [HPV]-negative oropharynx squamous cell carcinoma) * Any tumor with suspected PI3K-pathway dependence (either by mutation or by known biologic rationale, such as endometrial cancer; KRAS and PI3K dependence includes the presence of a PIK3CA-mutant hotspot mutation (such as E542 [K], E545 [A, G, or K], H1047 [L, R, Y]), PIK3CA copy number gain, or PTEN loss in the archival or fresh tumor tissue specimen identified in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory; all genetic findings must be reviewed by the study principal investigator [PI], prior to study entry) * A tumor previously treated with combined CDK4/6 and MEK inhibition that was progression-free for at least 4 months
  • 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)
  • 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 computed tomography (CT) scan
  • Participants are permitted to have any number of prior therapies prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9.0 gm/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (=< 5.0 X institutional upper limit of normal permitted if hepatic metastases present)
  • Creatinine within 1.5 x the ULN institutional limits
  • Fasting glucose =< 126 mg/dL (7.0 mmol/L)
  • Hemoglobin (Hb)A1c =< 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • 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 adverse events (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 palbociclib dose and during study treatment
  • Corrected QT interval (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
  • 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; baseline viral assessment is not required in patients with no known infection
  • 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 (e.g., raloxifene, valproic acid, propofol, propranolol, dapagliflozin, darexaban, mycophenolic acid, and tapentadol)
  • Acetaminophen use within 24 hours before a dose of gedatolisib (PF-05212384)
  • Concurrent use of herbal preparations including saw palmetto
  • Current use of drugs that are known to prolong QT interval
  • Proton pump inhibitor: the concomitant use of proton-pump inhibitors (including, but not limited to, dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) with palbociclib is prohibited; recommendations about the use of antacids or H2-receptor antagonists include, but not limited to: cimetidine, famotidine, nizatidine, and ranitidine; if needed, administer H2-receptor antagonists with a staggered dosing regimen (twice daily); the dosing of palbociclib should occur at least 10 hours after H2-receptor antagonist evening dose and 2 hours before the H2-receptor antagonist morning dose; local antacids: as acid lowering agents, local antacids may decrease palbociclib absorption and exposure; however, if needed, local antacids should be given at least 2 hours before or at least 2 hours after palbociclib administration


Beth Israel Deaconess Medical Center
Status: ACTIVE
Contact: James W. Mier
Phone: 617-667-0430
Brigham and Women's Hospital
Status: ACTIVE
Contact: Geoffrey Ira Shapiro
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Geoffrey Ira Shapiro
Massachusetts General Hospital Cancer Center
Status: ACTIVE
Contact: Rebecca Suk Heist
Phone: 617-726-1838


I. Determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, and tolerability of the combination of palbociclib and gedatolisib (PF-05212384). (Part I)

II. Determine the rate of progression free survival (PFS) > 4 months and the median PFS for the combination of palbociclib and gedatolisib (PF-05212384) in expansion cohorts. (Part II)

III. Further evaluate the safety, tolerability, and toxicity profile for the combination of palbociclib and gedatolisib (PF-05212384). (Part II)


I. Evaluate the pharmacokinetic (PK) properties for the combination of palbociclib and gedatolisib (PF-05212384). (Part I)

II. Confirm target engagement of palbociclib and gedatolisib (PF-05212384) in pre- and on-treatment tumor biopsies from patients enrolled to an MTD expansion cohort. (Part I)

III. Evaluate the preliminary clinical efficacy of palbociclib and gedatolisib (PF-05212384) in advanced solid tumors. (Part I)

IV. Evaluate the response rate, as determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), for the combination of palbociclib and gedatolisib (PF-05212384) in expansion cohorts. (Part II)

OUTLINE: This is a dose-escalation study.

Patients receive gedatolisib IV over 30 minutes once weekly (QW) on days 1, 8, and 15, and palbociclib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Geoffrey Ira Shapiro

  • Primary ID 16-499
  • Secondary IDs NCI-2017-00434
  • ID NCT03065062