A Trial of Pembrolizumab and Metformin Versus Pembrolizumab Alone in Advanced Melanoma

NCT03311308 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCC 16-196
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effectiveness and safety of the combination of Pembrolizumab (KEYTRUDA®) and the investigational drug, Metformin.

Conditions

Advanced Melanoma

Keywords

Melanoma; Unresectable; Stage III; Stage IV

Outcome Measures

Primary Outcomes (1)

• Ki-67 proliferation index in T cell

  determine the cell cycle status

  up to 4 years

Secondary Outcomes (6)

• Number of participants experiencing adverse events

  up to 4 years

• Hypoxia in the primary tumor by IHC Staining

  up to 4 years

• Mitochondrial functional restoration in Tumor Infiltrating Lymphocytes by mitochondrial mass

  up to 4 years

• Cell cycle status of peripheral blood T lymphocytes by Flow Cytometry

  up to 4 years

• overall tumor response rate

  up to 4 years

Other Outcomes (8)

• Functional restoration of peripheral blood T lymphocytes

  up to 4 years

• Progression free survival

  up to 5 years

• Correlating hypoxia measurements in the tumor with FDG avidity on PET.

  up to 4 years

Study Arms (2)

Pembrolizumab

ACTIVE COMPARATOR

Pembrolizumab (Keytruda), 200 mg, by IV, every three weeks, for up to 2 years; after the first three doses, dosing can be changed to 400mg IV every 6 weeks, at the treating physician's discretion.

Drug: Pembrolizumab Injection [Keytruda]

Pembrolizumab and Metformin Combination

EXPERIMENTAL

Pembrolizumab (Keytruda), 200mg, by IV, every three weeks, for up to 2 years will be taken in combination with Metformin, 500mg, twice a day, for nine weeks; after the first three doses, pembrolizumab dosing can be changed to 400mg IV every 6 weeks, at the treating physician's discretion.

Drug: Pembrolizumab Injection [Keytruda]; Drug: Metformin

Interventions

Pembrolizumab Injection [Keytruda] DRUG

200mg, IV, every three weeks, up to two years; After the first three doses, dosing can be changed to 400mg IV every 6 weeks, at the treating physician's discretion.

Also known as: Keytruda

Pembrolizumab; Pembrolizumab and Metformin Combination

Metformin DRUG

500 mg, by mouth, twice a day for nine weeks.

Pembrolizumab and Metformin Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Have un-resectable (stage III) or advanced (stage IV) melanoma.
• Be 18 years of age or older on day of signing informed consent
• Have measurable disease based on RECIST 1.1. Patients without measurable disease may be included on study after discussion with the Sponsor, given that the primary endpoint of the study is Ki-67 of TIL (flow cytometry)
• Have biopsiable disease. Be willing to provide tissue from a newly obtained biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on Day 1.
• Patients may have received prior adjuvant therapy with anti-PD-1, anti-CTLA-4, or BRAF/MEK inhibitors.
• Patients may be immunotherapy treatment naïve in the advanced setting or may be on anti-PD-1 therapy with SD or PR for at least 12 weeks. Patients may have received ipilimumab plus nivolumab in the metastatic setting with SD or PR for at least 12 weeks on maintenance anti-PD1.
• Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
• Have a baseline HbA1c ≤ 6.4.
• Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculateda creatinine clearance ≤1.5 X upper limit of normal (ULN) (GFR can also be used in place of creatinine or CrCl ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN)
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN

You may not qualify if:

• Has a current confirmed diagnosis of type 1 diabetes or type 2 diabetes that has been diagnosed by an HbA1c ≥6.5, or is on any hypoglycemic medications (insulin, metformin, etc). Patients with a screening HbA1c 6.5-7.0 may be included after discussion with the principal investigator. Patients currently on metformin will be excluded.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (this excludes patients on anti-PD1) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxineor physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic IV antibiotic therapy.
• 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 known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Yana Najjar: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Univ of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Metformin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Yana Najjar, Md

  Universtiy of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yana Najjar, MD

CONTACT

412-692-4724; najjaryg@upmc.edu

Amy Rose, RN

CONTACT

412-647-8587; kennaj@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: October 17, 2017
• Study Start: February 7, 2018
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (1)