Durvalumab With or Without Metformin in Treating Participants With Head and Neck Squamous Cell Carcinoma

NCT03618654 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 18P.389JT 12752
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial studies how well durvalumab given with or without metformin works in treating participants with head and neck squamous cell carcinoma. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread. Metformin, a drug typically used for the treatment of diabetes, may help to reduce the metabolic activity of cancer cells and of surrounding supportive tissues. It is not yet known whether giving durvalumab with or without metformin may work better in treating participants with head and neck squamous carcinoma.

Conditions

Head and Neck Squamous Cell Carcinoma; Oral Cavity Squamous Cell Carcinoma; Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Immune cell polarization (Th1/Th2; M1/M2)

  The biomarker data will be compared for differences in means (or geometric means) between treatment arms using Student's t-tests on the raw data (or on log-transformed data depending on the degree and nature of skew in the data). Non-parametric alternatives, such as permutation tests, will be considered if the data are not approximately normal for any continuous outcome variables after log-transformation. A similar approach will be used for making pre vs. post treatment comparisons, when necessary, but with paired t-tests or their non-parametric alternatives. The response outcomes will be evaluated between treatment arms by Fisher's exact tests.

  Up to 6 months

Secondary Outcomes (4)

• Alterations in immunohistochemical (IHC) markers

  Up to 6 months

• Alterations in intratumoral immune cell populations

  Up to 6 months

• Changes of the intratumoral immunophenotype and metabolism after exposure to durvalumab and metformin

  Baseline up to 6 months

• Tumor size as measured by immune-related response criteria (irRC)

  Up to 4 weeks post-treatment

Other Outcomes (4)

• Assessment of alterations in metabolites produced in different tumor compartments

  Up to 6 months

• Assessment of the interactions between the immune and metabolic microenvironments

  Up to 6 months

• Circulating Tumor DNA

  Baseline up to 12 days post surgery

Study Arms (2)

Arm A (durvalumab, metformin)

EXPERIMENTAL

Patients will take Metformin 500mg/day for 3 days. From day 4, 500mg twice daily and then in 3 days (day 7) dose escalation to 1000mg twice daily will be achieved. This will be taken until the day before surgery after dinner. Patients will receive 1500mg durvalumab (MEDI4736) via IV infusion

Drug: Metformin; Biological: Durvalumab

Arm B (durvalumab)

EXPERIMENTAL

Patients will receive 1500mg durvalumab (MEDI4736) via IV infusion. Participants receive durvalumab as in Arm A in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab

Interventions

Metformin DRUG

Given PO

Also known as: 1,1-Dimethylbiguanide, 657-24-9, N,N-Dimethylimidodicarbonimidic Diamide

Arm A (durvalumab, metformin)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Kappa-chain, Human Monoclonal MEDI4736 Heavy Chain, MEDI4736, Immunoglobulin G1

Arm A (durvalumab, metformin); Arm B (durvalumab)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed head and neck squamous cell carcinoma (HNSCC), with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Any stage HNSCC of the 1) oral cavity, 2) oropharynx, 3) larynx, 4) hypopharynx, 5) nasal cavity/paranasal sinuses, 6) unknown primary, 7) skin considered to have resectable disease. Patients with recurrent disease that is amenable to surgery are eligible
• Performance status 0-1
• Must have a life expectancy of at least 12 weeks as judged by the treating physician
• Body weight \>30 kg
• Absolute neutrophil count 1500/ul or more
• Platelets 100,000/ul or more
• Hemoglobin 9 g/dl or more
• Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \<3 mg/dl)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x the upper limit of normal
• Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or measured creatinine clearance using 24 hours urine collection
• Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]), which must also be confirmed as negative within 28 days of the start of study drugs
• Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 90 days after the last dose of study drugs. "Women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
• Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year. Men who are receiving the study medications will be instructed to adhere to contraception for 90 days after the last dose of study drugs. Men who are azoospermic do not require contraception
• Informed consent: All subjects must be able to comprehend and sign a written informed consent document

You may not qualify if:

• Patients with nasopharyngeal carcinoma or salivary gland primaries
• Any history of a sever hypersensitivity reaction to any monoclonal antibody
• Any history of allergy to the study drug components
• Any prior history of exposure to an anti PD-L1including durvalumab or PD1-directed therapy
• Patients who are already taking metformin, or who have taken metformin in the preceding 4 weeks
• Diabetic patients who are managed by taking metformin or insulin
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of durvalumab
• \* Note: Local surgery of isolated lesions for palliative intent and biopsy procedures are acceptable
• Subjects who are on medication that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations; current recommendations reflect caution when metformin is used with insulin, sulfonylureas, and iodinated contrast dye
• Mean QT interval corrected for heart rate (QTc) greater than or equal to 470 ms calculated from 3 electrocardiograms (EKGs) using Fridericia's Correction
• Any concurrent malignancies; exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin of a secondary location, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 2 years post-diagnosis
• Any diagnosis of immunodeficiency or receiving systemic steroid therapy with a dose of \>10 mg prednisone per day or equivalent or any other form of immunosuppressive therapy within 14 days of initiation of therapy, or a prior history of allogenic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Curry J, Alnemri A, Philips R, Fiorella M, Sussman S, Stapp R, Solomides C, Harshyne L, South A, Luginbuhl A, Tuluc M, Martinez-Outschoorn U, Argiris A, Linnenbach A, Johnson J. CD8+ and FoxP3+ T-Cell Cellular Density and Spatial Distribution After Programmed Death-Ligand 1 Check Point Inhibition. Laryngoscope. 2023 Aug;133(8):1875-1884. doi: 10.1002/lary.30389. Epub 2022 Sep 20.

  PMID: 36125263 DERIVED

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Metformin; durvalumab; Immunoglobulin G

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joseph Curry, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 7, 2018
• Study Start: November 1, 2018
• Primary Completion: November 20, 2021
• Study Completion: December 7, 2022
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

US (1)