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.
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
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
75
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.
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.
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
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.
Time frame: 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).
Time frame: 2 years
Progression Free Survival Rate at 4 months
Evaluate the preliminary clinical efficacy of palbociclib and gedatolisib in the following expansion cohorts: 1) advanced squamous cell lung cancer, 2) advanced pancreatic cancer, 3) advanced head \& neck cancer, and 4) any tumor with presumed PI3K-pathway dependence using CT and MRI scans per RECIST version 1.
Time frame: 4 months
Target engagement of palbociclib and gedatolisib in paired tumor biopsies
Confirm target engagement of palbociclib and gedatolisib in pre- and on-treatment tumor biopsies from patients enrolled to the MTD expansion cohort through evaluation of changes in immunohistochemical staining for parameters of CDK and PI3K activity.
Time frame: 2 years
Pharmacokinetic parameter (maximum concentration [Cmax]) of gedatolisib in the absence or presence of palbociclib
Time frame: 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
Time frame: 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
Time frame: 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 parameters (maximum concentration [Cmax]) of palbociclib in the presence of gedatolisib
Time frame: At 1, 2, 4, 6, 8, 10, and 24 hours after dosing (cycle 1 day 15)
Pharmacokinetic parameters (area under the curve [AUC]) of palbociclib in the presence of gedatolisib
Time frame: At 1, 2, 4, 6, 8, 10, and 24 hours after dosing (cycle 1 day 15)
Pharmacokinetic parameters (half-life [t1/2]) of palbociclib in the presence of gedatolisib
Time frame: At 1, 2, 4, 6, 8, 10, and 24 hours after dosing (cycle 1 day 15)
Overall Response Rate
Evaluate the preliminary clinical efficacy of palbociclib and gedatolisib in advanced solid tumors using CT and MRI scans per RECIST version 1.
Time frame: 2 years
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