Phase Ib/II study of metformin in combination with carboplatin/paclitaxel chemotherapy in patients with advanced ovarian cancer

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 124

Inclusion Criteria

•Patients with advanced stage (FIGO III-IV), histologically confirmed and documented epithelial ovarian carcinoma
•Patients eligible for neoadjuvant carboplatin/paclitaxel chemotherapy prior to surgical debulking (phase 1 or 2) OR patients with relapsed or progressive ovarian cancer after initial treatment eligible for palliative carboplatin/paclitaxel chemotherapy (phase 1 only)
•Measurable tumour according to RECISTv1.1 or GCIG CA125 criteria (phase 2 only)
•Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0-2
•Age >= 18 years
•Adequate blood count, hepatic and renal function
•Written informed consent

Exclusion Criteria

•Prior chemotherapy, immunotherapy, targeted agents or radiotherapy to abdomen or pelvis (phase 2 only)
•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.
•Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer (phase 2 only)
•Symptomatic CNS metastasis
•Pre-existing peripheral neuropathy >= 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary end-point of the phase I study is the recommended phase II dose<br /><br>based on dose-limiting toxicities and maximum tolerated dose of metformin in<br /><br>combination with carboplatin/paclitaxel.<br /><br><br /><br>The primary end-point of the phase II study is objective response rate in<br /><br>patients with measureable disease and CA-125 response as defined by the<br /><br>Gynaecologic Cancer Intergroup (GCIG) for non-measurable disease.</p><br>

Secondary Outcome Measures