Brenner TumorPhase 2NCT02122185
Metformin and Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
A Phase 2 study testing metformin hydrochloride and Chemotherapy in people with Brenner Tumor and Malignant Ascites, run by University of Chicago at 10 sites in United States.
Trial summary
This randomized phase II trial studies how well metformin hydrochloride and combination chemotherapy works in treating patients with stage III-IV ovarian, fallopian tube, or primary peritoneal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Brenner Tumor, Malignant Ascites, Malignant Pleural Effusion
- What is being tested?
- metformin hydrochloride and Chemotherapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 111 participants
- Where
- 10 sitesUnited States
- Study dates
- 25 Feb 2015to 8 Oct 2024
- Phase
- Phase 2
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ELIGIBILITY CRITERIA FOR PRE-REGISTRATION
- A reasonable suspicion of ovarian cancer by the treating oncologist is required, evidenced by abdominal carcinomatosis, omental caking, pleural effusions or ascites AND an elevated CA125 > 250 OR CA125:carcinoembryonic antigen (CEA) ratio > 25 OR CA125 =< 250 with no evidence of gastrointestinal (GI) cancer
- Aged 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
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- Platelets >= 100,000/mcL
- Total bilirubin =< upper normal institutional limits (except for patients with Gilbert's disease who are eligible despite elevated serum bilirubin level)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 × institutional upper limit of normal
- Creatinine =< institutional upper limit of normal (ULN) OR creatinine clearance >= 60 mL/min/1.73 m^2
- Blood glucose =< 126 mg/dL fasting or =< 140 mg/dL nonfasting
- Signed written pre-registration informed consent document
- ELIGIBILITY CRITERIA FOR REGISTRATION:
- Histologically confirmed carcinoma consistent with ovarian, fallopian tube, or primary peritoneal carcinoma
- Subjects undergoing primary debulking surgery must have stage III or IV disease and have undergone surgery to include, at a minimum, removal of the uterus, ovaries and fallopian tubes; these patients may be optimally debulked (less than 1 cm residual disease) but must have grossly visible macroscopic residual disease OR be suboptimally debulked
- Subjects for whom neoadjuvant chemotherapy followed by interval cytoreductive surgery is planned must have fine needle aspirate (FNA) or other cytology showing adenocarcinoma OR core biopsies OR surgically directed biopsies showing adenocarcinoma AND CA125 over 250 OR CA125:CEA ratio > 25 OR CA =< 250 with no evidence of GI cancer; they should have presumed stage III or IV disease, generally based on abdominal carcinomatosis, omental caking, pleural effusions or ascites
- Subject and her physician must agree to six cycles or up to 8 cycles of one of the standard of care regimens allowed on this protocol; these regimens (starting dosage) include:
- If < 70 years old:
- IV paclitaxel 175 mg/m^2 and carboplatin area under the curve (AUC) 5-6 every 21 days
- IV docetaxel 75 mg/m^2 and carboplatin AUC 5-6 every 21 days
- IV paclitaxel 80 mg/m^2 day 1, 8, and 15 and carboplatin AUC 5-6 day 1 every 21 days
- If 70 years or older:
- IV paclitaxel 135 mg/m^2 plus IV carboplatin AUC 5 plus optional G-CSF every 21 days
- IV paclitaxel 60 mg/m^2 day 1, 8, 15 plus IV carboplatin AUC 5 every 21 days (Day 15 paclitaxel optional)
- IV paclitaxel 60 mg/m^2 plus IV carboplatin AUC 2 day 1, 8, and 15 every 21 days
- ECOG performance status =< 2
- Leukocytes >= 3,000/mcL
- absolute neutrophil count >= 1,500/mcL
- platelets >= 100,000/mcL
- total bilirubin =< upper normal institutional limits (except for patients with Gilbert's disease who are eligible despite elevated serum bilirubin level)
- AST(SGOT)/ALT(SGPT) =< 2.0 × institutional upper limit of normal
- creatinine =< OR institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
- blood glucose =< 126 mg/dL fasting or =< 140 mg/dL nonfasting
- women of child-bearing potential must agree to use an effective method of birth control on trial, as the safety of metformin in pregnancy has not been established; an effective method of birth control includes surgical sterilization of woman or her partner, abstinence, or two barrier methods (e.g. condom plus diaphragm); hormonal methods of birth control are not permitted on this study
- ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Subjects with known diabetes and those taking metformin, sulfonylureas, thiazolidinediones or insulin for any reason
- Patients who are receiving any other investigational agents
- Subjects with comorbidities that would limit their two year survival for reasons other than ovarian cancer
- Concurrent active invasive malignancy or one previously diagnosed with a greater than 30% chance of recurrence in the next two years
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin
- Subjects must not have conditions associated with increased risk of metformin-associated lactic acidosis, including New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, alcoholic liver disease, or habitual intake of 3 or more alcoholic beverages per day
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active major infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or nursing women
- mucinous adenocarcinoma, borderline tumors
- subjects who will undergo intraperitoneal chemotherapy
- subjects receiving neoadjuvant chemotherapy for whom interval debulking surgery (assuming adequate response to therapy) is not planned
- subjects receiving chemotherapy regimens not specified in the inclusion criteria
- subjects should not be participating in other clinical trials of interventions designed to reduce risk of ovarian cancer recurrence or plan to receive off -protocol maintenance therapy (e.g. paclitaxel or bevacizumab)
- subjects with known diabetes, fasting glucose over 126 mg/dL or random glucose over 140 mg/dL and those taking metformin, sulfonylureas, thiazolidenediones or insulin for any reason
- patients who are receiving any other investigational agents
- subjects with comorbidities which would lead to a clinical expectation that they will not survive two years for reasons other than ovarian cancer
- concurrent active invasive malignancy or one previously diagnosed with a greater than 30% chance of recurrence in the next two years
- history of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin
- subjects must not have conditions associated with increased risk of metformin-associated lactic acidosis, including New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, alcoholic liver disease, or habitual intake of 3 or more alcoholic beverages per day
- uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- pregnant or nursing women
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
NCH Medical Group- Northwest Community Hospital
Arlington Heights, Illinois, 60005
University of Alabama
Birmingham, Alabama, 35233
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
Decatur Memorial Hospital
Decatur, Illinois, 62526
City of Hope
Duarte, California, 91010
NorthShore University HealthSystem
Evanston, Illinois, 60201
Ingalls Memorial Hospital
Harvey, Illinois, 60426
Mitchell Cancer Institute - University of South Alabama
Mobile, Alabama, 36604
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: A Randomized Placebo Controlled Phase II Trial of Metformin in Conjunction With Chemotherapy Followed by Metformin Maintenance Therapy in Advanced Stage Ovarian, Fallopian Tube and Primary Peritoneal Cancer
This randomized phase II trial studies how well metformin hydrochloride and combination chemotherapy works in treating patients with stage III-IV ovarian, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride may help carboplatin, paclitaxel and docetaxel work better by making tumor cells more sensitive to the drugs. Studying samples of blood and tissue in the laboratory from patients receiving metformin hydrochloride may help doctors learn more about the effects of metformin hydrochloride on cells. It may also help doctors understand how well patients respond to treatment. Giving metformin hydrochloride together with combination chemotherapy may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine if the addition of metformin to standard adjuvant or neoadjuvant chemotherapy plus extended metformin (metformin hydrochloride) beyond standard chemotherapy increases progression free survival when compared to 6 cycles of standard chemotherapy alone in non-diabetic subjects with stage III (with any gross residual disease) or stage IV ovarian, primary peritoneal, or fallopian tube carcinoma.
SECONDARY OBJECTIVES:
- To determine whether the addition of metformin to standard chemotherapy plus extended metformin beyond standard chemotherapy increases the time to biochemical progression when compared to chemotherapy alone.
II. To compare biochemical (cancer antigen [CA]-125) response rates in the two arms.
III. To describe and compare toxicities in the two arms. IV. To compare overall survival in both arms.
TERTIARY OBJECTIVES:
- To elucidate metformin's molecular mechanism of action in ovarian, fallopian tube or primary peritoneal cancer by: determining whether metformin's anti-cancer effects are mediated by systemic metabolic changes, a direct effect on tumor cells, or both, and testing the metabolic and proteomic alterations induced in biospecimens from non-diabetic patients prospectively treated with standard chemotherapy in conjunction with metformin compared to placebo.
OUTLINE:
Patients receive a standard chemotherapy regimen at the discretion of the treating physician. Regimens include either paclitaxel intravenously (IV) over 2-3 hours and carboplatin IV over 30-60 minutes on day 1; docetaxel IV over 1 hour on and carboplatin IV over 30-60 minutes on day 1; or paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 6 courses. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive metformin hydrochloride orally (PO) twice daily (BID) and standard chemotherapy regimen as above for 6 courses. Treatment for metformin hydrochloride continues for up to 2 years in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo PO BID and standard chemotherapy regimen as above for 6 courses. Treatment for placebo continues for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
- Conditions
- Brenner Tumor, Malignant Ascites, Malignant Pleural Effusion, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mixed Epithelial Carcinoma
- Being tested
- metformin hydrochloride, placebo, Chemotherapy
- Medical subject headings
- Brenner Tumor, Pleural Effusion, Malignant, Fallopian Tube Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin hydrochlorideDrug
Also called Glucophage
Given PO
placeboDrug
Also called PLCB
Given PO
ChemotherapyDrug
Participants will receive standard chemotherapy (6-8 cycles). Specific regimen to be given was chosen from among six protocol-specified options at the discretion of their treating physician.
| Study group | Role | What they receive |
|---|---|---|
| Metformin plus chemotherapy | Experimental | Patients receive metformin hydrochloride PO BID and standard chemotherapy for 6 -8 cycles. Treatment with metformin hydrochloride continues for up to 2 years in the absence of disease progression or unacceptable toxicity. Receives: Drug: metformin hydrochloride; Drug: Chemotherapy |
| Placebo plus chemotherapy | Placebo comparator | Patients receive placebo PO BID and standard chemotherapy for 6 -8 cycles. Treatment with placebo continues for up to 2 years in the absence of disease progression or unacceptable toxicity. Receives: Drug: placebo; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Time to disease progression or death from any cause. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 and Gynecological Cancer Intergroup (GCIG) criteria. For example, progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 6 years
Secondary outcomes (3)
Time to Biochemical (CA-125) Progression, Radiological Progression, or Death.
CA125 progression determined using GCIG criteria. Radiological progression assessed using RECIST criteria as described above for PFS. For example, progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 6 years
Overall Survival
Time from randomization to death.
Measured: Up to 6 years
Number of Participants With Adverse Events
Grade 3 or higher serious adverse event. Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2014 (estimated)
- Study start25 Feb 2015
- Primary completion27 Oct 2022
- Study completion8 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brenner TumorStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Seiko Yamada, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02122185
- Sponsor's protocol ID
- IRB13-1235
- Other IDs
- NCI-2014-00860, IRB13-1235
- Status last verified
- Mar 2026
- First submitted
- 22 Apr 2014
- Last updated
- 27 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes