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

NCT02312661 | Completed Phase 1 DMC

• 1 other identifier: 30102012
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Epithelial Ovarian Cancer

Keywords

ovarian cancer; metformin; carboplatin; paclitaxel

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events as a measure of safety and tolerability

  Data will be used to determine recommended phase 2 dose

  1-2 years

Secondary Outcomes (1)

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

  1-2 years

Study Arms (1)

Carboplatin / paclitaxel /metformin

EXPERIMENTAL

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

Drug: Metformin; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Metformin DRUG

Metformin in increasing doses will be added to carboplatin/paclitaxel chemotherapy

Carboplatin / paclitaxel /metformin

Carboplatin DRUG

Intravenous carboplatin chemotherapy in three-weekly cycles, for a maximum of 6 cycles

Carboplatin / paclitaxel /metformin

Paclitaxel DRUG

Intravenous paclitaxel chemotherapy in three-weekly cycles, for a maximum of 6 cycles

Carboplatin / paclitaxel /metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Mecdical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Ovarian Neoplasms

Interventions

Metformin; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2014
• First Posted: December 9, 2014
• Study Start: October 5, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: May 6, 2024

Record last verified: 2024-05

Locations

NL (1)