Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

• Status: Active, not recruiting
• Trial end date: 2023-09-13
• Target enrollment: 0
• Participant gender: Female

Summary

This randomized phase II/III trial studies how well paclitaxel, carboplatin, and metformin hydrochloride works and compares it to paclitaxel, carboplatin, and placebo in treating patients with endometrial cancer that is stage III, IV, or has come back. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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 paclitaxel and carboplatin work better by making cancer cells more sensitive to the drugs. It is not yet known whether paclitaxel and carboplatin is more effective with or without metformin hydrochloride in treating endometrial cancer.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gynecologic Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Treatments: Albumin-Bound Paclitaxel; Carboplatin; Metformin; Paclitaxel

Criteria

Inclusion Criteria:

• Patients must have measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma

• Histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible:

• Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.)

• Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than 1.4 mg/dl

• Bilirubin less than or equal to 1.5 x institutional/laboratory upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Patients must NOT have received prior chemotherapy or targeted therapy, including chemotherapy used for radiation sensitization for treatment of endometrial carcinoma

• Patients may have received prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy

• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy

• Patients must be able to swallow and retain orally-administered medication

• Patients must have signed an approved informed consent and authorization permitting release of personal health information; individuals with impaired decision-making capacity are not eligible to participate on the study

Exclusion Criteria:

• Patients must NOT be taking metformin or have been on metformin in the past 6 months

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the last three years

• 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

• Patients who are pregnant or nursing; if patients are of reproductive age and have not undergone hysterectomy, they must use an effective contraceptive method for the duration of this study

• Any condition associated with increased risk of metformin-associated lactic acidosis; (e.g. congestive heart failure defined as New York Heart Association [NYHA] class III or IV functional status, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day)