800-872-2273

Clinical Trials and Studies

Your participation matters. Help us discover and cure!

Contact us at (800) USC-CARE (800-872-2273)

We're sorry, but this trial is no longer enrolling volunteers.

A Randomized Phase II/III Study of Paclitaxel/Carboplatin/Metformin (NSC#91485) versus Paclitaxel/Carboplatin/Placebo as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer

Description

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. Metformin hydrochloride may help paclitaxel and carboplatin work better by making cancer cells more sensitive to the drugs. Objective: The primary ojective is to determine if the addition of metformin (metformin hydrochloride) to the standard regimen of carboplatin and paclitaxel prolongs progression-free survival (PFS) in women with advanced or recurrent endometrial cancer. Study Population: Women, 18 years or older with Stage III or IVA endometrial cancer with measurable disease Stage IVB endometrial cancer, recurrent endometrial cancer and no prior chemotherapy. Study Arms: Arm 1: Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Metformin 850 mg oral QD, beginning on day 1. If tolerated for 4 weeks, the dose will be increased to Metformin 850 mg BID. Every 21 days x 6 cycles. Maintenance regimen (for patients in complete response, partial response or stable disease) Metformin 850 mg oral BID (one cycle of maintenance therapy = 21 days) Arm 2: Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Placebo for metformin 850 mg oral QD, beginning on day 1. If tolerated for 4 weeks, the dose will be increased to placebo for metformin 850 mg BID. Every 21 days x 6 cycles. Maintenance regimen (for patients in complete response, partial response or stable disease) Matched placebo oral BID (one cycle of maintenance therapy = 21 days) Outcomes: Progression-free survival (PFS), (Phase II) [ Time Frame: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years ] Follow-up: Follow-up every 3 months for 2 years and then every 6 months for 3 years. Follow-up forms are collected for the 5 year follow-up period or until study termination. Statistics: This study will use an intent-to-treat principle with equal randomization to each treatment arm, balanced by performance status (0 or 1 versus 2), disease status (Stage III versus Stage IV or recurrent), and patient body mass index (BMI < 30 versus >=30). The study will accrue 240 patients and test the equivalence of PFS between the regimens after 60 PFS events are observed in the reference regimen at a 20% level of significance. Analysis: Assuming no interruption of accrual, this analysis will be conducted approximately when 60% of the targeted accrual is attained. If the futility analysis indicates a higher hazard of death on the experimental arm, then the trial could close at that time.

Phase

N/A

Inclusion and Exclusion 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

  • 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)

Sites

Please contact Carryl Du Bois to learn more about where you can participate in this trial. Please use the contact form on the right side.

Powered by SC CTSI