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Head and Neck Squamous Cell CarcinomaEarly Phase 1NCT03618654

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

A Early Phase 1 study testing Metformin and Durvalumab in people with Head and Neck Squamous Cell Carcinoma and Oral Cavity Squamous Cell Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Metformin and Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
1 Nov 2018to 7 Dec 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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
  • Subjects who have received iodinated contrast dye less than 12 hours prior to screening meet a temporary exclusion criterion to receive metformin. These patients cannot start investigational metformin until 12 hours have elapsed from contrast administration. Subjects who are scheduled for iodinated contrast dye are not excluded but will be asked to hold their doses prior to dye administration
  • 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 unresolved toxicity National Cancer Institute NCI Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician
  • 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
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Patients must not be receiving any other investigational agents
  • Receipt of a live attenuated vaccine within 30 days prior to the first dose of drug on trial
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
  • Patients must not be pregnant or breastfeeding
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B virus (HBV) (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Window of Opportunity for Durvalumab (MEDI4736) Plus Metformin Trial of in Squamous Cell Carcinoma of the Head and Neck

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate the combined effect of metformin and durvalumab on the immune tumor microenvironment, specifically with respect to alterations in T cell polarization (Th1/Th2 ratio) and tumor associated macrophage (TAM) (M1/M2 ratio) as measured by cytokine shifts in tumor specimens and peripheral blood.

SECONDARY OBJECTIVES:

  1. To investigate the combined effect of metformin and durvalumab on the metabolic microenvironment, specifically with respect to alterations in immunohistochemical markers of the reverse Warburg effect.

II. To further characterize the alterations in intratumoral immune cell populations (effector T cells [Teff], regulatory T cells [Tregs], tumor associated macrophages [TAMs], and myeloid-derived suppressor cells [MDSC]).

III. To assess changes of the intratumoral immunophenotype and metabolism after exposure to durvalumab and metformin by transcriptome analysis using a ribonucleic acid-sequencing (RNA-seq) transcriptome analysis.

IV. To assess the efficacy of combined durvalumab and metformin treatment prior to surgery as determined by radiographic response and immune-related response criteria (irRC).

  1. To assess the safety and tolerability of the combination of metformin and durvalumab.
Being tested
Metformin, Durvalumab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called 1,1-Dimethylbiguanide, 657-24-9, N,N-Dimethylimidodicarbonimidic Diamide

    Given PO

  • DurvalumabBiological

    Also called Imfinzi, Kappa-chain, Human Monoclonal MEDI4736 Heavy Chain, MEDI4736

    Given IV

Study groups in NCT03618654
Study groupRoleWhat they receive
Arm A (durvalumab, metformin)ExperimentalPatients 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
Receives: Drug: Metformin; Biological: Durvalumab
Arm B (durvalumab)ExperimentalPatients will receive 1500mg durvalumab (MEDI4736) via IV infusion. Participants receive durvalumab as in Arm A in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 6 months

Secondary outcomes (4)

  1. Alterations in immunohistochemical (IHC) markers

    Pre- and post-treatment patient tumor samples will be compared. The study will compare data from patients treated with durvalumab and metformin to patients treated with Durvalumab alone and to patients from our own historical controls of head and neck squamous carcinoma (HNSCC), both untreated and treated with metformin monotherapy

    Measured: Up to 6 months

  2. Alterations in intratumoral immune cell populations

    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.

    Measured: Up to 6 months

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

    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.

    Measured: Baseline up to 6 months

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

    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.

    Measured: Up to 4 weeks post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2018
  2. Study start1 Nov 2018
  3. Primary completion20 Nov 2021
  4. Study completion7 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03618654
Sponsor's protocol ID
18P.389
Other IDs
JT 12752
Status last verified
May 2025
First submitted
1 Aug 2018
Last updated
15 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 36125263

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Metformin and Durvalumab in people with Head and Neck Squamous Cell Carcinoma and Oral Cavity Squamous Cell Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University 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 15 inclusion and 25 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: finished, as of the sponsor's last update on 15 May 2025. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune cell polarization (Th1/Th2; M1/M2) (time frame: Up to 6 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 NCT03618654, which also lists 1 linked publication.

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 15 May 2025.

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