Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT04114136

Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies

Led by Dan Zandberg · Updated on 2026-04-24

72

Participants Needed

1

Research Sites

367 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Patients with histologically or cytologically confirmed advanced melanoma, renal cell carcinoma, NSCLC, HCC (Child Pugh Class A only), MSI-High solid tumors, Urothelial Cancer, GE junction/Gastric Adenocarcinoma, or HNSCC for which current standard of care treatment for their stage of disease would be with Pembrolizumab or Nivolumab monotherapy, who meet eligibility criteria will undergo a biopsy (core or excisional/incisional; FNA not adequate) for baseline tissue. Patients will then be randomized to one of 3 arms: Anti-PD-1 mAb plus Metformin 500mg po BID, Anti-PD-1 mAb alone, Anti-PD-1 mAb plus Rosiglitazone 4mg po qdaily. Five weeks (+/- 7 days) after initiation of therapy a patient will undergo a repeat biopsy (core or excisional/incisional; FNA not adequate) for correlative analysis. The patient will then continue on study therapy for up to 2 years, or until progression of disease or unacceptable toxicity, whichever occurs first. RECIST 1.1 with modifications, to allow for continued therapy until progressive disease is confirmed if the patient is clinically stable, will be used in the trial.

CONDITIONS

Official Title

Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Adults aged 18 years or older
  • Histologically or cytologically confirmed advanced melanoma, renal cell carcinoma, NSCLC, hepatocellular carcinoma (Child Pugh Class A only), MSI-High solid tumors, urothelial cancer, GE junction/gastric adenocarcinoma, or head and neck squamous cell carcinoma
  • Accessible tumor for pretreatment and post-treatment biopsy via core or surgical biopsy (excisional/incisional); fine needle aspiration is not adequate
  • At least one measurable area of disease based on RECIST 1.1
  • ECOG performance status 0 to 2
  • Normal organ and marrow function including absolute neutrophil count ≥1,500/mcL, platelets ≥100,000/mcL, total bilirubin ≤ institutional upper limit of normal, AST/ALT ≤2.5 × institutional upper limit of normal, creatinine clearance ≥40 mL/min/1.73 m²
  • Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to first dose
  • Female subjects of childbearing potential must agree to use one method of birth control or abstain from heterosexual activity during the study and for 120 days after last dose
  • Male subjects must agree to use adequate contraception during the study and for 120 days after last dose
  • Ability to understand and sign informed consent
  • If known prior brain metastases, no active or enlarging symptomatic brain disease on MRI/CT
  • Type II diabetes patients not requiring prescription diabetes medication and no use of metformin, insulin, sulfonylureas or thiazolidinediones within 60 days prior to study start
Not Eligible

You will not qualify if you...

  • Prior treatment with anti-PD-1 or anti-PD-L1 monoclonal antibody therapy
  • Type I diabetes or use of metformin, insulin, sulfonylureas, or thiazolidinediones within 60 days prior to study start
  • Pregnancy or breastfeeding; women of childbearing potential must use birth control and have a negative pregnancy test within 7 days before first dose
  • Active autoimmune disease requiring systemic treatment within past 3 months or history of severe autoimmune disease, except stable conditions like vitiligo or resolved childhood asthma
  • Uncontrolled cardiac disease or symptomatic heart failure (NYHA Class III or IV)
  • Psychiatric illness or social issues limiting compliance
  • History of non-infectious pneumonitis requiring steroids or current active non-infectious pneumonitis
  • Use of non-approved or investigational drugs within 14 days prior to study treatment
  • Prior malignancy within 2 years except certain treated skin, cervical, or prostate cancers
  • Conditions or lab abnormalities that could interfere with trial participation
  • Known HIV infection
  • Hypersensitivity to study drugs (metformin, rosiglitazone, pembrolizumab, or nivolumab)
  • Unable to take oral pills or feeding tube medications
  • History of acidosis or heavy alcohol intake (5 or more drinks daily)
  • Requirement for active treatment with Rifampin or Gemfibrozil for other conditions

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

1
2
3
+1

Trial Site Locations

Total: 1 location

1

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

Actively Recruiting

Loading map...

Research Team

J

Jennifer Ruth, RN, BSN

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

3

Not the Right Trial for You?

Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.

Already have an account? Log in here