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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

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

A Phase II Clinical Trial of Anti-PD-1 mAb Therapy Alone or With Metabolic Modulators to Reverse Tumor Hypoxia and Immune Dysfunction in Solid Tumor Malignancies

Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies (NCT04114136) is a Phase 2 interventional studying Melanoma and NSCLC, sponsored by Dan Zandberg. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Melanoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 72 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Melanoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. diagnosed by tissue sample (biopsy-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. 2. Accessible tumor for pretreatment (baseline) and post treatment biopsy. Tumor must be accessible for core or surgical biopsy (excisional/incisional), FNA is not adequate 3. Age ≥ 18 years 4. Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1. 5. You should be able to carry out daily activities with 0 level of ability (ECOG 0)-2 6. Patients must have normal organ and marrow function as defined below: absolute neutrophil count ≥1,500/mcL platelet count at least 100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN kidney function (creatinine clearance) at least 40 mL/min/1.73 m2 7. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Female subjects of childbearing potential should be willing to use one methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 10. Ability to understand and the willingness to sign a written willing to sign a consent form document ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. 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. 2. Accessible tumor for pretreatment (baseline) and post treatment biopsy. Tumor must be accessible for core or surgical biopsy (excisional/incisional), FNA is not adequate 3. Age ≥ 18 years 4. Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1. 5. ECOG performance status 0-2 6. Patients must have normal organ and marrow function as defined below: absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN Creatinine clearance ≥40 mL/min/1.73 m2 7. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Female subjects of childbearing potential should be willing to use one methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 10. Ability to understand and the willingness to sign a written informed consent document 11. If known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI/CT evaluation. 12. A type II DM patient who does not currently require prescription medication for diabetes treatment and has not received metformin, insulin, sulfonylureas or thiazolidinediones within 60 days of the start of study treatment can be enrolled on the study. Exclusion Criteria: 1. Treatment with prior anti-PD-1 or anti-PD-L1 mAb therapy 2. Patients with type I DM or any patient who has received metformin, insulin, sulfonylureas, or thiazolidinediones within 60 days of start of study treatment for any reason. 3. Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study must be informed of the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. 4. All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. 5. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. 6. History of uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months) 7. Symptomatic heart failure or New York Heart Association Class III or IV heart failure 8. Psychiatric illness or other social issues limiting compliance 9. Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis. 10. Treatment with a non-approved or investigational drug within 14 days prior to Day 1 of study treatment. 11. Prior malignancy within 2 years with the exception of adequately treated basal cell or squamous cell skin cancer, carcinoma of the cervix or prostate cancer. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Per Medical History Review 14. Hypersensitivity to metformin, rosiglitazone, pembrolizumab or nivolumab 15. Unable to take in pills either orally or via feeding tube 16. History of acidosis of any type or habitual intake of 5 or more alcoholic beverages a day. 17. Patients that require active treatment with Rifampin or Gemfibrozil for other medical conditions.

Treatments Being Tested

DRUG

Nivolumab or Pembrolizumab (dependent upon approved indication)

Anti-PD-1 mAb (monoclonal antibody)

DRUG

Metformin

Acts directly or indirectly on the liver to lower glucose production, and acts on the gut to increase glucose utilisation, increase GLP-1 and alter the microbiome.

DRUG

Rosiglitazone

A member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ).

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04114136), the sponsor (Dan Zandberg), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04114136 clinical trial studying?

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 … The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04114136?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04114136?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04114136. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04114136. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.