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NCT02325401

Dose-finding Study of Metformin With Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma

Completed Phase 1 Results posted Last updated 11 June 2020
What this trial tests

Phase 1 trial testing Metformin in Head and Neck Cancer in 20 participants. Completed in 21 February 2020.

Timeline
11 May 2015
Primary endpoint
26 December 2017
21 February 2020

Quick facts

Lead sponsorUniversity of Cincinnati
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment20
Start date11 May 2015
Primary completion26 December 2017
Estimated completion21 February 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Cincinnati

Who can join

18 and older, any sex, with Head and Neck Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) of Metformin in Combination With Concurrent Cisplatin and Radiation Primary · 24 months

Cohorts of patients received escalating doses of metformin (2000 mg, 2550 mg, or 3000 mg divided into daily doses) with a 7-day to 14-day lead-in prior to CRT based on the modified toxicity probability interval design to allow for possible re-escalation after previous de-escalation and to maximize the ability to identify the maximum tolerated dose (MTD). Patients continued to receive metformin for the duration of CRT as tolerated.

GroupValue95% CI
Metformin (2000mg) With ChemoradiationNA
Metformin (2550mg) With ChemoradiationNA
Metformin (3000mg) With ChemoradiationNA
Number of Participants Experiencing No-Reoccurrence at 36 Months Secondary · 36 months

Patients were evaulated at 36 months to determine if there was recurrence of disease.

GroupValue95% CI
Metformin (2000mg) With Chemoradiation6
Metformin (2550mg) With Chemoradiation8
Metformin (3000mg) With Chemoradiation4
Number of Participants With Adverse Events Secondary · 36 months

Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.Any participants with any adverse event at any grade was included. Adverse events were collected during the on study period of 21 weeks up to three months after the study for a total of 34 weeks.

GroupValue95% CI
Metformin (2000mg) With Chemoradiation6
Metformin (2550mg) With Chemoradiation7
Metformin (3000mg) With Chemoradiation4
Progression Free Survival Secondary · 24 months

2-year progression free survival

GroupValue95% CI
Metformin (2000mg) With Chemoradiation6
Metformin (2550mg) With Chemoradiation8
Metformin (3000mg) With Chemoradiation4
Overall Survival Secondary · 24 months

2 year overall survival

GroupValue95% CI
Metformin (2000mg) With Chemoradiation5
Metformin (2550mg) With Chemoradiation8
Metformin (3000mg) With Chemoradiation4

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected during the on study period of 21 weeks up to three months after the study for a total of 34 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Metformin With Chemoradiation- 2000mg Cohort
Serious: 6/6 (100%)
Deaths: 1/6
Metformin With Chemoradiation- 2550mg Cohort
Serious: 1/8 (13%)
Deaths: 0/8
Metformin With Chemoradiation- 3000mg Cohort
Serious: 1/4 (25%)
Deaths: 0/4

Serious adverse events (9 terms)

ReactionSystemMetformin With Chemoradiat…Metformin With Chemoradiat…Metformin With Chemoradiat…
Lung infectionRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
SyncopeNervous system disorders
Febrile NeutropeniaBlood and lymphatic system disorders
Mucositis OralGastrointestinal disorders
Acute Kidney InjuryRenal and urinary disorders
Creatinine IncreasedBlood and lymphatic system disorders
Neutrophil count decreasedBlood and lymphatic system disorders
Other adverse events (58 terms — click to expand)

ReactionSystemMetformin With Chemoradiat…Metformin With Chemoradiat…Metformin With Chemoradiat…
Acute Kidney InjuryRenal and urinary disorders
NauseaGastrointestinal disorders
TinnitusEar and labyrinth disorders
AnemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
DysphagiaGastrointestinal disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
White blood cell decreasedInvestigations
Alanine aminotransferase increasedHepatobiliary disorders
Creatinine increaseHepatobiliary disorders
DysgeusiaGastrointestinal disorders
Gastroesophageal reflux diseaseGastrointestinal disorders
HoarsenessRespiratory, thoracic and mediastinal disorders
HyperglycemiaMetabolism and nutrition disorders
ThrushInfections and infestations
InsomniaPsychiatric disorders
OdynophagiaInvestigations
Mucositis oralGastrointestinal disorders
Neutrophil count decreasedInvestigations
OdgnophagiaRespiratory, thoracic and mediastinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders
Abdominal PainGastrointestinal disorders
Acute Kidney DiseaseRenal and urinary disorders
Alkaline phosphatase increasedHepatobiliary disorders
Back PainMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
DepressionPsychiatric disorders
Dry MouthGastrointestinal disorders
Ear PainEar and labyrinth disorders
Edema TrunkGeneral disorders
FeverGeneral disorders
HeadacheNervous system disorders
Hearing impairedEar and labyrinth disorders
HiccupsRespiratory, thoracic and mediastinal disorders
HyperkalemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders

Most-reported serious reactions: Lung infection, Atrial fibrillation, Hypoxia, Syncope, Febrile Neutropenia, Mucositis Oral, Acute Kidney Injury, Creatinine Increased.

Data from ClinicalTrials.gov NCT02325401 adverse events section.

Sponsor's own description

The purpose of this research study is to test the safety of adding metformin to standard of care. The standard of care treatment will be cisplatin once every 3 weeks for 3 treatments and radiation for 7 weeks. Metformin is a medication that is currently used to treat diabetes. Increasing amounts of metformin will be given to groups of patients already receiving normal treatment for their cancer to see if metformin causes any good effects by killing your cancer or bad effects (side effects).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The updated landscape of tumor microenvironment and drug repurposing.
    Jin MZ, Jin WL. · · 2020 · cited 900× · PMID 32843638 · DOI 10.1038/s41392-020-00280-x
  2. Repurposing metformin for cancer treatment: current clinical studies.
    Chae YK, Arya A, Malecek MK, Shin DS, et al · · 2016 · cited 233× · PMID 27004404 · DOI 10.18632/oncotarget.8194
  3. Drug repurposing for cancer therapy.
    Xia Y, Sun M, Huang H, Jin WL. · · 2024 · cited 229× · PMID 38637540 · DOI 10.1038/s41392-024-01808-1
  4. Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma.
    Cai Y, Dodhia S, Su GH. · · 2017 · cited 67× · PMID 28108737 · DOI 10.18632/oncotarget.14729
  5. Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition.
    Crist M, Yaniv B, Palackdharry S, Lehn MA, et al · · 2022 · cited 61× · PMID 36328378 · DOI 10.1136/jitc-2022-005632
  6. mTOR co-targeting strategies for head and neck cancer therapy.
    Wang Z, Valera JC, Zhao X, Chen Q, et al · · 2017 · cited 52× · PMID 28822012 · DOI 10.1007/s10555-017-9688-7
  7. Autophagy Modulators in Cancer Therapy.
    Buzun K, Gornowicz A, Lesyk R, Bielawski K, et al · · 2021 · cited 50× · PMID 34071600 · DOI 10.3390/ijms22115804
  8. Metformin: A Dual-Role Player in Cancer Treatment and Prevention.
    Galal MA, Al-Rimawi M, Hajeer A, Dahman H, et al · · 2024 · cited 44× · PMID 38612893 · DOI 10.3390/ijms25074083

Verify or expand the search:

Other trials of Metformin

Trials testing the same drug.

Other recruiting trials for Head and Neck Cancer

Currently open trials in the same condition.

Other University of Cincinnati trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02325401.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing