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Study of Metformin With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer (OVMET)

Primary Purpose

Epithelial Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Metformin
Carboplatin
Paclitaxel
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring ovarian cancer, metformin, carboplatin, paclitaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with advanced stage (FIGO III-IV), histologically confirmed and documented epithelial ovarian carcinoma
  • Patients eligible for neo-adjuvant carboplatin/paclitaxel chemotherapy prior to surgical debulking OR patients with relapsed or progressive ovarian cancer after initial treatment eligible for palliative carboplatin/paclitaxel chemotherapy
  • Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0-2
  • Age ≥ 18 years
  • Laboratory Requirements - within 7 days prior to enrolment:
  • absolute neutrophil count (ANC) ≥1.5 x 109/L
  • platelets > 100 x 109/L
  • hemoglobin >9g/dl. Patients may be transfused or use erythropoietin to maintain hemoglobin values ≥ 9 g/dl.
  • hepatic function: bilirubin ≤1.5×upper limit of normal (ULN), aspartate aminotransferase (AST)/ALT≤2.5×ULN
  • estimated creatinine clearance ≥ 60ml/min
  • Before patient registration/randomization, written informed consent for the trial must be given according to International Conference on Harmonisation (ICH)/ good clinical practice (GCP), and national/local regulations.

Exclusion Criteria:

  • Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study.
  • Metformin within 4 weeks prior to enrolment.
  • Symptomatic central nervous system (CNS) metastasis
  • Pre-existing peripheral neuropathy ≥ Common toxicity criteria (CTC) grade 2.
  • Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start.
  • Women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the study and for 6 months after the last study medication.
  • Known hypersensitivity to any of the study drugs or excipients.
  • Serious active infection requiring i.v. antibiotics at enrolment.
  • Unstable medical conditions.
  • Evidence of any other medical conditions, physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications.

Sites / Locations

  • University Mecdical Center Groningen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carboplatin / paclitaxel /metformin

Arm Description

Three-weekly cycles of carboplatin/paclitaxel chemotherapy in combination with metformin treatment

Outcomes

Primary Outcome Measures

Number of participants with Adverse Events as a measure of safety and tolerability
Data will be used to determine recommended phase 2 dose

Secondary Outcome Measures

Pharmacokinetics (AUC, Tmax,Cmax) of carboplatin and paclitaxel chemotherapie

Full Information

First Posted
November 28, 2014
Last Updated
April 6, 2018
Sponsor
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT02312661
Brief Title
Study of Metformin With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer
Acronym
OVMET
Official Title
Phase Ib Study of Metformin in Combination With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
October 5, 2015 (Actual)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Molecularly targeted agents which inhibit the mammalian target of rapamycin (mTOR) pathway and/or circumvent p53 in the induction of apoptosis are exciting potential targets in ovarian cancer. Metformin is a biguanide, widely used in the treatment of type 2 diabetes mellitus, that has shown anti-cancer activity in preclinical studies. The main mechanism of metformin's effect is mTOR pathway inhibition and, in addition, it has been shown to circumvent p53-induced apoptosis making it an exciting, potentially effective drug in ovarian cancer.
Detailed Description
A phase Ib, single-centre, dose-escalation trial with a traditional escalation rule with fixed dose levels ("3 + 3" rule). The recommended phase II dose will be defined as the maximum predefined dose level at which 0 of 3 or ≤ 1 of 6 subjects experience a drug-related dose limiting toxicity (DLT) during cycle 1 and 2 of treatment. An estimated 10-20 patients will be required for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Ovarian Cancer
Keywords
ovarian cancer, metformin, carboplatin, paclitaxel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carboplatin / paclitaxel /metformin
Arm Type
Experimental
Arm Description
Three-weekly cycles of carboplatin/paclitaxel chemotherapy in combination with metformin treatment
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin in increasing doses will be added to carboplatin/paclitaxel chemotherapy
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Intravenous carboplatin chemotherapy in three-weekly cycles, for a maximum of 6 cycles
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Intravenous paclitaxel chemotherapy in three-weekly cycles, for a maximum of 6 cycles
Primary Outcome Measure Information:
Title
Number of participants with Adverse Events as a measure of safety and tolerability
Description
Data will be used to determine recommended phase 2 dose
Time Frame
1-2 years
Secondary Outcome Measure Information:
Title
Pharmacokinetics (AUC, Tmax,Cmax) of carboplatin and paclitaxel chemotherapie
Time Frame
1-2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with advanced stage (FIGO III-IV), histologically confirmed and documented epithelial ovarian carcinoma Patients eligible for neo-adjuvant carboplatin/paclitaxel chemotherapy prior to surgical debulking OR patients with relapsed or progressive ovarian cancer after initial treatment eligible for palliative carboplatin/paclitaxel chemotherapy Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0-2 Age ≥ 18 years Laboratory Requirements - within 7 days prior to enrolment: absolute neutrophil count (ANC) ≥1.5 x 109/L platelets > 100 x 109/L hemoglobin >9g/dl. Patients may be transfused or use erythropoietin to maintain hemoglobin values ≥ 9 g/dl. hepatic function: bilirubin ≤1.5×upper limit of normal (ULN), aspartate aminotransferase (AST)/ALT≤2.5×ULN estimated creatinine clearance ≥ 60ml/min Before patient registration/randomization, written informed consent for the trial must be given according to International Conference on Harmonisation (ICH)/ good clinical practice (GCP), and national/local regulations. Exclusion Criteria: Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study. Metformin within 4 weeks prior to enrolment. Symptomatic central nervous system (CNS) metastasis Pre-existing peripheral neuropathy ≥ Common toxicity criteria (CTC) grade 2. Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. Women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the study and for 6 months after the last study medication. Known hypersensitivity to any of the study drugs or excipients. Serious active infection requiring i.v. antibiotics at enrolment. Unstable medical conditions. Evidence of any other medical conditions, physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications.
Facility Information:
Facility Name
University Mecdical Center Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands

12. IPD Sharing Statement

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Study of Metformin With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer

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