MelanomaPhase 2NCT04114136
Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies
A Phase 2 study testing Nivolumab or Pembrolizumab (dependent upon approved indication), Metformin and Rosiglitazone in people with Melanoma and NSCLC, run by Dan Zandberg at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, NSCLC, Hepatocellular Carcinoma
- What is being tested?
- Nivolumab or Pembrolizumab (dependent upon approved indication), Metformin and Rosiglitazone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2020to 30 Apr 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Accessible tumor for pretreatment (baseline) and post treatment biopsy. Tumor must be accessible for core or surgical biopsy (excisional/incisional), FNA is not adequate
- Age ≥ 18 years
- Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1.
- ECOG performance status 0-2
- Patients must have normal organ and marrow function as defined below:
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- 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
- 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.
- 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.
- 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.
- Ability to understand and the willingness to sign a written informed consent document
- If known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI/CT evaluation.
- 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.
Who cannot join
- Treatment with prior anti-PD-1 or anti-PD-L1 mAb therapy
- 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.
- 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.
- 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.
- 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.
- History of uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months)
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- Symptomatic heart failure or New York Heart Association Class III or IV heart failure
- Psychiatric illness or other social issues limiting compliance
- Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
- Treatment with a non-approved or investigational drug within 14 days prior to Day 1 of study treatment.
- 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.
- 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.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Per Medical History Review
- Hypersensitivity to metformin, rosiglitazone, pembrolizumab or nivolumab
- Unable to take in pills either orally or via feeding tube
- History of acidosis of any type or habitual intake of 5 or more alcoholic beverages a day.
- Patients that require active treatment with Rifampin or Gemfibrozil for other medical conditions.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Jennifer Ruth, RN, BSN, 412-623-8963, ruthj2@upmc.edu
Dan P Zandberg, MD
About this study
Official title: 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
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.
Read the detailed description
The prognosis for patients with metastatic disease remains poor. The use of immunotherapy in the treatment of cancer is based on the premise that tumors evade the endogenous immune response by being recognized as self, and not non-self. The recent success of immune-modulating agents in patients with refractory solid tumors has provided proof-of-concept of the efficacy of immune system activation as a therapeutic modality. Tumors develop immune resistance using different mechanisms; the goal of immunotherapy is to counteract these resistance mechanisms, allowing the endogenous immune system to reject tumors. One of those mechanisms of resistance is tumor hypoxia
This study aims to examine whether Metformin and Rosiglitazone will reduce tumor oxygen consumption, creating a less hypoxic T cell environment, with pharmacologic remodeling of the TME leading to restored anti-tumor T cell effector function and as a result will act synergistically with anti-PD-1 mAb resulting in a higher response rate than with anti-PD-1 mAb alone. The safety and tolerability of if adding metformin or rosiglitazone to anti-PD-1 mAb therapy will assessed.
Eligible patients will undergo pre-treatment biopsy and then will be randomized to one of three arms: 1. Anti-PD-1 mAb + Metformin 500mg PO BID 2. Anti-PD-1 mAb alone or 3. Anti-PD-1 mAb plus Rosiglitazone 4mg po qdaily. Patients will undergo post treatment biopsy after 5 weeks (+/- 7 days) of treatment and then continue treatment for up to 2 years, or until progression of disease or unacceptable toxicity, whichever occurs first.
- Conditions
- Melanoma, NSCLC, Hepatocellular Carcinoma, Urothelial Cancer, Gastric Adenocarcinoma, HNSCC
- Being tested
- Nivolumab or Pembrolizumab (dependent upon approved indication), Metformin, Rosiglitazone
- Keywords
- Anti-PD-1 monoclonal antibody (mAb), tumor infiltrating lymphocytes (TIL)
- Medical subject headings
- Melanoma, Carcinoma, Hepatocellular, Squamous Cell Carcinoma of Head and Neck, Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab or Pembrolizumab (dependent upon approved indication)Drug
Also called Opdivo (nivolumab) or Keytruda (pembrolizumab)
Anti-PD-1 mAb (monoclonal antibody)
MetforminDrug
Also called Glucophage, Glucophage XR, Fortamet, and Glumetza
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.
RosiglitazoneDrug
Also called Avandia
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).
| Study group | Role | What they receive |
|---|---|---|
| Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Metformin | Experimental | nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator)
Metformin - 500 mg by mouth twice daily Receives: Drug: Nivolumab or Pembrolizumab (dependent upon approved indication); Drug: Metformin |
| Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Rosiglitazone | Experimental | nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator)
Rosiglitazone - 4 mg by mouth once daily Receives: Drug: Nivolumab or Pembrolizumab (dependent upon approved indication); Drug: Rosiglitazone |
| Anti-PD-1 mAb (nivolumab or pembrozilumab) | Active comparator | nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator) Receives: Drug: Nivolumab or Pembrolizumab (dependent upon approved indication) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best overall response
Best overall response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), by tumor type, recorded from the start of the treatment until disease progression/recurrence. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Incomplete Response/Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, (reference smallest sum diameters). Progressive Disease (PD): ≥ 20% increase in the sum of diameters of target lesions (reference smallest sum diameters); the sum must also demonstrate an absolute increase of at least 5 mm; (appearance ≥ 1 new lesions is considered progression).
Measured: From start of the treatment until disease progression/recurrence up to 48 months
Secondary outcomes (3)
Progression-free survival (PFS)
The length of time after study enrollment that patients lives without experiencing disease progression per RECIST v1.1. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 48 months
Overall Survival (OS)
The length of time after study enrollment that patients remain alive.
Measured: Up to 48 months
Number of Participants Experiencing Adverse Events Attributed to Treatment
Participants experiencing adverse events (per CTCAE v5.0) that are possibly, probably or definitely related to study treatment, will be tabulated by category, grade and relatedness.
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2019
- Study start14 Sep 2020
- Primary completion30 Apr 2032 (estimated)
- Study completion30 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dan Zandberg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dan Zandberg, University of Pittsburgh
- Investigators
- Dan P Zandberg, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04114136
- Sponsor's protocol ID
- HCC 18-190
- Status last verified
- Jun 2026
- First submitted
- 26 Sep 2019
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Giannitti G, Paganoni AJJ, Marchesi S, Garavaglia R, Fontana F. Mitochondrial bioenergetics and networks in melanoma: an update. Apoptosis. 2025 Oct;30(9-10):2042-2056. doi: 10.1007/s10495-025-02155-4. Epub 2025 Jul 28.
PubMed 40721981Zandberg DP, Menk AV, Velez M, Normolle D, DePeaux K, Liu A, Ferris RL, Delgoffe GM. Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck. J Immunother Cancer. 2021 May;9(5):e002088. doi: 10.1136/jitc-2020-002088.
PubMed 33986123
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04114136
- Acronym / sponsor ID
- HCC 18-190
- Conditions
- Melanoma, NSCLC, Hepatocellular Carcinoma, Urothelial Cancer, Gastric Adenocarcinoma, HNSCC
- Keywords
- Anti-PD-1 monoclonal antibody (mAb), tumor infiltrating lymphocytes (TIL)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Dan ZandbergUniversity, hospital or other
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 30 Apr 2032 (estimated)
- Study completion
- 30 Apr 2032 (estimated)
- First posted
- 3 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The prognosis for patients with metastatic disease remains poor. The use of immunotherapy in the treatment of cancer is based on the premise that tumors evade the endogenous immune response by being recognized as self, and not non-self. The recent success of immune-modulating agents in patients with refractory solid tumors has provided proof-of-concept of the efficacy of immune system activation as a therapeutic modality. Tumors develop immune resistance using different mechanisms; the goal of immunotherapy is to counteract these resistance mechanisms, allowing the endogenous immune system to reject tumors. One of those mechanisms of resistance is tumor hypoxia
This study aims to examine whether Metformin and Rosiglitazone will reduce tumor oxygen consumption, creating a less hypoxic T cell environment, with pharmacologic remodeling of the TME leading to restored anti-tumor T cell effector function and as a result will act synergistically with anti-PD-1 mAb resulting in a higher response rate than with anti-PD-1 mAb alone. The safety and tolerability of if adding metformin or rosiglitazone to anti-PD-1 mAb therapy will assessed.
Eligible patients will undergo pre-treatment biopsy and then will be randomized to one of three arms: 1. Anti-PD-1 mAb + Metformin 500mg PO BID 2. Anti-PD-1 mAb alone or 3. Anti-PD-1 mAb plus Rosiglitazone 4mg po qdaily. Patients will undergo post treatment biopsy after 5 weeks (+/- 7 days) of treatment and then continue treatment for up to 2 years, or until progression of disease or unacceptable toxicity, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Metformin | Experimental | Drug: Nivolumab or Pembrolizumab (dependent upon approved indication), Drug: Metforminnivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator) Metformin - 500 mg by mouth twice daily |
| Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Rosiglitazone | Experimental | Drug: Nivolumab or Pembrolizumab (dependent upon approved indication), Drug: Rosiglitazonenivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator) Rosiglitazone - 4 mg by mouth once daily |
| Anti-PD-1 mAb (nivolumab or pembrozilumab) | Active comparator | Drug: Nivolumab or Pembrolizumab (dependent upon approved indication)nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- Accessible tumor for pretreatment (baseline) and post treatment biopsy. Tumor must be accessible for core or surgical biopsy (excisional/incisional), FNA is not adequate
- Age ≥ 18 years
- Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1.
- ECOG performance status 0-2
Key exclusion criteria (17 listed)
- Treatment with prior anti-PD-1 or anti-PD-L1 mAb therapy
- 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.
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab or Pembrolizumab (dependent upon approved indication)Also: Opdivo (nivolumab) or Keytruda (pembrolizumab)Anti-PD-1 mAb (monoclonal antibody) | Drug | Anti-PD-1 mAb (nivolumab or pembrozilumab), Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Metformin, Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Rosiglitazone |
| MetforminAlso: Glucophage, Glucophage XR, Fortamet, and GlumetzaActs 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 | Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Metformin |
| RosiglitazoneAlso: AvandiaA 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). | Drug | Anti-PD-1 mAb (nivolumab or pembrozilumab) plus Rosiglitazone |
Primary outcome
Best overall response
Time frame: From start of the treatment until disease progression/recurrence up to 48 months
Best overall response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), by tumor type, recorded from the start of the treatment until disease progression/recurrence. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Incomplete Response/Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, (reference smallest sum diameters). Progressive Disease (PD): ≥ 20% increase in the sum of diameters of target lesions (reference smallest sum diameters); the sum must also demonstrate an absolute increase of at least 5 mm; (appearance ≥ 1 new lesions is considered progression).
3 secondary outcomes
Progression-free survival (PFS)
Time frame: Up to 48 months
Overall Survival (OS)
Time frame: Up to 48 months
Number of Participants Experiencing Adverse Events Attributed to Treatment
Time frame: Up to 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Derived from this study: PubMed 40721981Giannitti G, Paganoni AJJ, Marchesi S, Garavaglia R, Fontana F. Mitochondrial bioenergetics and networks in melanoma: an update. Apoptosis. 2025 Oct;30(9-10):2042-2056. doi: 10.1007/s10495-025-02155-4. Epub 2025 Jul 28.
- Derived from this study: PubMed 33986123Zandberg DP, Menk AV, Velez M, Normolle D, DePeaux K, Liu A, Ferris RL, Delgoffe GM. Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck. J Immunother Cancer. 2021 May;9(5):e002088. doi: 10.1136/jitc-2020-002088.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dan P Zandberg principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab or Pembrolizumab (dependent upon approved indication), Metformin and Rosiglitazone in people with Melanoma and NSCLC, run by Dan Zandberg at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Ruth, RN, BSN (412-623-8963, ruthj2@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best overall response (time frame: From start of the treatment until disease progression/recurrence up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04114136, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.