A Phase 2 interventional study of Metformin in Ovarian, Fallopian Tube, and Primary Peritoneal Cancer, sponsored by University of Michigan Rogel Cancer Center. Completed at 1 site in United States. Open to female participants aged 19 Years to 79 Years. Per ClinicalTrials.gov, last updated 2018-05-25.
Sponsored by University of Michigan Rogel Cancer Center · Phase 2, Interventional, and Treatment
The primary objective of this study is to determine if metformin administered in combination with chemotherapy to women with advanced ovarian, primary peritoneal or fallopian tube cancer will improve recurrence-free survival at 18 months compared to controls.
Despite 70% remission rates with surgery and chemotherapy, the majority of patients with stage III/IV ovarian cancer will relapse and die of their disease. This is consistent with a cancer stem cell (CSC) model in which a few residual treatment resistant stem cells persist and initiate disease recurrence. Laboratory studies indicate therapies targeting CSC will greatly improve cancer outcomes. We have recently characterized a population of CSC in ovarian cancer. Importantly, similar to that observed in breast cancer, we have found that the diabetes drug metformin can restrict ovarian CSC growth and proliferation. In addition metformin increases tumor cell sensitivity to chemotherapy. Consistent with this, epidemiologic studies demonstrate that diabetic patients with ovarian cancer taking metformin have better outcomes than those not taking metformin. However, metformin has not been tested as an anti-cancer stem cell agent in ovarian cancer. Thus we propose to perform a phase II clinical trial using metformin as an anti-cancer stem cell agent in ovarian cancer patients. Patients who plan to receive primary surgical debulking will initiate metformin therapy prior to surgery and then continue after surgery along with chemotherapy. Patients who will be treated neoadjuvantly will initiate metformin with chemotherapy prior to surgery and then continue both metformin and chemotherapy after surgery. Tumor specimens will be acquired for all patients at the time of primary surgery. The primary objective of this study will be to determine if metformin improves the recurrence-free survival (RFS) of patients relative to historical controls. Secondary objectives of this study will be: (a) to compare the amount of CSC in primary tumor specimens in metformin treated patients versus matched controls from our tumor bank, (b) to determine if metformin improves overall survival relative to historical controls, (c) to confirm the safety of metformin in non-diabetic ovarian cancer patients, and (d) as laboratory studies indicate that metformin is most active in p53 mutant cells and p53 is mutated in \~50% of ovarian cancers, we will assess whether response rates correlate with p53 mutation status. If successful, this well tolerated FDA approved drug could be immediately translated into phase III trials and impact patient outcomes.
361 studies on the registry are indexed under Peritoneal Neoplasms; 56 are open to participants now.
This study's enrollment of 90 is above the median of 45 across 288 interventional studies indexed under Peritoneal Neoplasms.
Browse Peritoneal Neoplasms studies →University of Michigan Rogel Cancer Center is the lead sponsor of 316 studies on the registry; 46 are open to participants now.
Of its 46 completed or terminated interventional studies of FDA-regulated products, 30 (65%) have results posted.
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Adequate liver function (bilirubin \< 1.5 times ULN).
Exclusion Criteria:
Drug: Metformin
Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy. Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
Also known as: Fortamet, Glucophage, Glumetza, Riomet
Recurrence-Free Survival
Determine the percentage of patients alive without recurrence at 18 months. Investigators will also determine recurrence free survival when patients with persistent disease are excluded. Definition of progression or recurrence and survival will be defined as increasing clinical, radiological or histological evidence of disease since study entry or two serum values of CA-125 greater than or equal to two times the upper limits of normal (ULN) performed at least one week apart, regardless of CT scan results. Recurrence-Free Interval will be defined as date from start of chemotherapy to the date of first clinical, biochemical, or radiological evidence of progression or death due to any cause.
Time frame: 18 months
Overall Survival
Determine the median overall survival time for all patients who complete treatment as well as for patients presenting with stage IIc/ III and stage IV ovarian cancer.
Time frame: Up to 3 Years
| Milestone | Metformin |
|---|---|
| Started | 90 |
| Completed | 38 |
| Not completed | 52 |
| Withdrew: Ineligible after treatment start | 40 |
| Withdrew: Patient choice | 3 |
| Withdrew: Noncompliance | 3 |
| Withdrew: Withdrawal by subject | 6 |
Determine the percentage of patients alive without recurrence at 18 months. Investigators will also determine recurrence free survival when patients with persistent disease are excluded. Definition of progression or recurrence and survival will be defined as increasing clinical, radiological or histological evidence of disease since study entry or two serum values of CA-125 greater than or equal to two times the upper limits of normal (ULN) performed at least one week apart, regardless of CT scan results. Recurrence-Free Interval will be defined as date from start of chemotherapy to the date of first clinical, biochemical, or radiological evidence of progression or death due to any cause.
| percentage of patients | Metformin - All Patients Analyzed | Metformin - Patients With Persistent Disease Excluded |
|---|---|---|
| Recurrence-Free Survival | 58.1 (38 to 73.8) | 55.6 (35.2 to 71.8) |
Determine the median overall survival time for all patients who complete treatment as well as for patients presenting with stage IIc/ III and stage IV ovarian cancer.
| months | Metformin - All Patients Analyzed | Metformin - Patients Stage IIc/ III Ovarian Cancer | Metformin - Patients With Stage IV Ovarian Cancer |
|---|---|---|---|
| Overall Survival | 43 (35 to 56) | 52 (35 to 65) | 36 (15 to 43) |
Collected over Up to 30 days post treatment. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin | 2/90 (2.2%) | 26/90 (28.9%) | 40/90 (44.4%) |
| Event | Metformin |
|---|---|
| AnemiaBlood and lymphatic system disorders | 6/90 |
| IleusGastrointestinal disorders | 6/90 |
| Platelet count decreasedInvestigations | 4/90 |
| White blood cell decreasedInvestigations | 3/90 |
| HyponatremiaMetabolism and nutrition disorders | 3/90 |
| Small intestinal obstructionGastrointestinal disorders | 2/90 |
| Lung infectionInfections and infestations | 2/90 |
| Neutrophil count decreasedInvestigations | 2/90 |
| Acute kidney injuryRenal and urinary disorders | 2/90 |
| HypotensionVascular disorders | 2/90 |
| Event | Metformin |
|---|---|
| AnemiaBlood and lymphatic system disorders | 26/90 |
| FatigueGeneral disorders | 17/90 |
| White blood cell decreasedInvestigations | 17/90 |
| DiarrheaGastrointestinal disorders | 13/90 |
| Platelet count decreasedInvestigations | 13/90 |
| NauseaGastrointestinal disorders | 12/90 |
| Neutrophil count decreasedInvestigations | 12/90 |
| Peripheral sensory neuropathyNervous system disorders | 9/90 |
| Abdominal painGastrointestinal disorders | 8/90 |
| Aspartate aminotransferase increasedInvestigations | 8/90 |
| Age, Continuous(years) | Metformin |
|---|---|
| Mean | 58 (30 to 79) |
| Sex: Female, Male(Participants) | Metformin |
|---|---|
| Female | 90 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | Metformin |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 69 |
| Unknown or Not Reported | 19 |
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University of Michigan Rogel Cancer Center