Ovarian, Fallopian Tube, and Primary Peritoneal CancerPhase 2NCT01579812
Evaluation of Metformin, Targeting Cancer Stem Cells for Prevention of Relapse in Gynecologic Patients
A Phase 2 study testing Metformin in people with Ovarian, Fallopian Tube, and Primary Peritoneal Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 to 79 years, women only
- Conditions the study is for
- Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 to 79 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with potential diagnosis of ovarian, fallopian, or primary peritoneal cancer.
- Care plan including surgical debulking and traditional adjuvant or neo-adjuvant chemotherapy (6-9 cycles of platinum and taxane based therapy).
- Eastern Cooperative Oncology Group performance status 0-2.
- Age > 18 years or < 80 years.
- Adequate renal function (serum creatinine <1.4mg/dL).
- Adequate liver function (bilirubin < 1.5 times ULN).
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- Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) < 5 times the upper limit of normal in case of liver metastases.
- ALT or AST < 2.5 times the ULN in absence of liver metastases.
- Ability to understand and complete written informed consent.
- Mentally, physically, and geographically able to undergo treatment and follow up.
Who cannot join
- Patients diabetes mellitus. (Patients with only a history of gestational diabetes will be allowed to be included in the study.)
- Metformin use in the last 6 months.
- A known hypersensitivity to metformin.
- A history of metabolic acidosis, including ketoacidosis or increased risk of lactic acidosis.
- Pregnancy or Lactation.
- Patients who have any severe and/or uncontrolled medical conditions.
Show all 9Show fewer
- Patients with a history of renal disease.
- Patients with other known active malignancy (excluding adequately treated basal cell / squamous cell skin cancer, in situ cancer, or other cancer for which the patient has been disease free for 2 years).
- Patients receiving any other investigational agents.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Evaluation of Metformin, Targeting Cancer Stem Cells for the Prevention of Relapse in Patients With Stage IIC/III/IV Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
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.
Read the detailed description
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.
- Being tested
- Metformin
- Keywords
- Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Fortamet, Glucophage, Glumetza, Riomet
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Not described Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Secondary outcomes (1)
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.
Measured: Up to 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2012 (estimated)
- Study startOct 2011
- Primary completionJun 2017
- Study completionJul 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian, Fallopian Tube, and Primary Peritoneal CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronald J. Buckanovich, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01579812
- Sponsor's protocol ID
- UMCC 2011.037
- Other IDs
- HUM 47900
- Status last verified
- May 2018
- First submitted
- 30 Mar 2012
- Last updated
- 25 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brown JR, Chan DK, Shank JJ, Griffith KA, Fan H, Szulawski R, Yang K, Reynolds RK, Johnston C, McLean K, Uppal S, Liu JR, Cabrera L, Taylor SE, Orr BC, Modugno F, Mehta P, Bregenzer M, Mehta G, Shen H, Coffman LG, Buckanovich RJ. Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer. JCI Insight. 2020 Jun 4;5(11):e133247. doi: 10.1172/jci.insight.133247.
PubMed 32369446
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Evaluation of Metformin, Targeting Cancer Stem Cells for the Prevention of Relapse in Patients With Stage IIC/III/IV Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
- ClinicalTrials.gov ID
- NCT01579812
- Acronym / sponsor ID
- UMCC 2011.037
- Keywords
- Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 18 Apr 2012 (estimated)
- Results
- Posted 25 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin |
Who may qualify
- Ages
- 19 to 79 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with potential diagnosis of ovarian, fallopian, or primary peritoneal cancer.
- Care plan including surgical debulking and traditional adjuvant or neo-adjuvant chemotherapy (6-9 cycles of platinum and taxane based therapy).
- Eastern Cooperative Oncology Group performance status 0-2.
- Age > 18 years or < 80 years.
- Adequate renal function (serum creatinine <1.4mg/dL).
Key exclusion criteria (9 listed)
- Patients diabetes mellitus. (Patients with only a history of gestational diabetes will be allowed to be included in the study.)
- Metformin use in the last 6 months.
- A known hypersensitivity to metformin.
- A history of metabolic acidosis, including ketoacidosis or increased risk of lactic acidosis.
- Pregnancy or Lactation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: Fortamet, Glucophage, Glumetza, RiometPatients 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. | Drug | Metformin |
Primary outcome
Recurrence-Free Survival
Time frame: 18 months
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.
1 secondary outcome
Overall Survival
Time frame: Up to 3 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32369446Brown JR, Chan DK, Shank JJ, Griffith KA, Fan H, Szulawski R, Yang K, Reynolds RK, Johnston C, McLean K, Uppal S, Liu JR, Cabrera L, Taylor SE, Orr BC, Modugno F, Mehta P, Bregenzer M, Mehta G, Shen H, Coffman LG, Buckanovich RJ. Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer. JCI Insight. 2020 Jun 4;5(11):e133247. doi: 10.1172/jci.insight.133247.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald J. Buckanovich, MD, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Ovarian, Fallopian Tube, and Primary Peritoneal Cancer, run by University of Michigan Rogel Cancer Center 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 10 inclusion and 9 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 25 May 2018. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Recurrence-Free Survival (time frame: 18 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 NCT01579812, 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 25 May 2018.