This phase II trial studies the effects of immunotherapy (pembrolizumab or nivolumab) alone, in combination with metformin, or in combination with rosiglitazone in treating malignant solid tumors that have spread to other parts of the body (advanced). Comparing the immune system to a car, there are two ways to make a car go faster. One is to press on the gas pedal and the other is to take the foot of the brake. The immune system has many “gas pedals” and “brakes” in order to help it decide whether to attack or not attack abnormal cells. Pembrolizumab and nivolumab are antibodies (a type of protein) that work by blocking a “brake” (akin to taking the foot off the brake in the car) on the immune system cells which may help the immune system attack the cancer. Metformin and rosiglitazone may change the amount of oxygen that is available to the immune system that is trying to attack the cancer. This allows the immune system to be more active. The purpose of this trial is to determine whether the addition of rosiglitazone or metformin to standard of care immunotherapy can cause cancer to respond (shrink in size) more than with immunotherapy alone.
Additional locations may be listed on ClinicalTrials.gov for NCT04114136.
Locations matching your search criteria
United States
Pennsylvania
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)Status: Active
Contact: Dan Paul Zandberg
Phone: 412-864-7955
PRIMARY OBJECTIVE:
I. Compare the probability of best overall response between anti-PD-1 monoclonal antibody (mAb) alone, anti-PD-1 mAb plus metformin, and anti-PD-1 mAb plus rosiglitazone stratified by tumor type.
SECONDARY OBJECTIVES:
I. To compare progression-free survival (PFS) and overall survival (OS) of anti-PD-1 mAb alone, anti-PD-1 mAb plus metformin, and anti-PD-1 mAb plus rosiglitazone, stratified by tumor type.
II. To determine the safety of the combination of anti-PD-1 mAb plus metformin and anti-PD-1 mAb plus rosiglitazone in the combined therapy arms.
EXPLORATORY CORRELATIVE OBJECTIVES:
I. To determine the cell cycle status (propidium iodide and Ki-67 staining by flow cytometry) of peripheral blood T lymphocytes in patients treated with anti-PD-1 mAb plus metformin and anti-PD-1 mAb plus rosiglitazone compared to patients treated with anti-PD-1 mAb alone.
II. To determine the degree of mitochondrial functional restoration (measured by mitochondrial mass and Seahorse metabolic profiling) in tumor infiltrating leukocytes (TIL) and peripheral blood lymphocytes (PBL) of patients treated with metformin plus anti-PD-1 mAb and rosiglitazone plus anti-PD-1 mAb compared to anti-PD-1 mAb alone (comparing before and after treatment) and correlate the degree of mitochondrial functional restoration with efficacy.
III. Evaluate oral and stool microbiome and correlate the baseline distribution and the change over time with efficacy.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A: Patients receive rosiglitazone orally (PO) once daily (QD) for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab intravenously (IV) every 4 weeks or pembrolizumab IV every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive nivolumab or pembrolizumab as in Arm A.
ARM C: Patients receive metformin PO twice daily (BID) for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab or pembrolizumab as in Arm A.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for year 1, every 6 months for year 2, and then annually.
Lead OrganizationUniversity of Pittsburgh Cancer Institute (UPCI)
Principal InvestigatorDan Paul Zandberg
