Doxorubicin Hydrochloride, Cisplatin, and Paclitaxel or Carboplatin and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

GOG Foundation

Status and phase: Completed; Phase 3

Conditions: Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer AJCC v7

Treatments: Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Biological: Filgrastim; Drug: Cisplatin; Biological: Pegfilgrastim; Drug: Carboplatin; Other: Quality-of-Life Assessment; Drug: Doxorubicin Hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00063999

U10CA027469 (U.S. NIH Grant/Contract)

U10CA180868 (U.S. NIH Grant/Contract)

NCI-2009-00584 (Registry Identifier)

CDR0000305940

GOG-0209 (Other Identifier)

Details and patient eligibility

About

This randomized phase III trial compares how well two different combination chemotherapy regimens (doxorubicin hydrochloride, cisplatin, and paclitaxel versus carboplatin and paclitaxel) work in treating patients with endometrial cancer that is stage III-IV or has come back (recurrent). Drugs used in chemotherapy such as doxorubicin hydrochloride, cisplatin, 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. It is not yet known which combination chemotherapy regimen is more effective in treating endometrial cancer.

Full description

PRIMARY OBJECTIVES:

I. To determine if the combination of carboplatin and paclitaxel (TC) chemotherapy is therapeutically equivalent to the combination of doxorubicin (doxorubicin hydrochloride), cisplatin and paclitaxel (TAP) chemotherapy with regards to survival.

II. To determine if estrogen/progesterone receptor status provides prognostic information in patients treated with chemotherapy.

III. To assess whether combination TC chemotherapy is superior to combination TAP chemotherapy with regards to toxicity profile, specifically neurotoxicity and infection.

IV. To measure differences in patient-reported neurotoxicity and quality of life (QOL) among the regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients with left ventricular ejection fraction < 50% at randomization who are initially randomized to Arm I are immediately crossed over to Arm II.

ARM I: Patients receive doxorubicin hydrochloride intravenously (IV) over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim subcutaneously (SC) on days 3-12 or pegfilgrastim SC on day 3.

ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1.

In both arms, treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Enrollment: 1,381 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have primary stage III or stage IV or recurrent endometrial carcinoma whose potential for cure by radiation therapy or surgery alone or in combination is very poor; pathological confirmation and estrogen receptor (ER)/progesterone receptor (PR) status of the primary tumor is mandatory; however, the results do not need to be available prior to registration
• Patients may not have received prior cytotoxic chemotherapy, including chemotherapy used for radiation sensitization; patients may have received prior radiation therapy, hormonal therapy, or therapy with biologic agents, but such therapies must be discontinued prior to entry on this study
• Patients in whom both radiation and chemotherapy is planned must receive radiation prior to entry on this study; at least four weeks should have elapsed since completion of radiation therapy (RT) involving the whole pelvis or over 50% of the spine
• Platelets >= 100,000/mcl
• Granulocytes (absolute neutrophil count [ANC]) >= 1,500/mcl
• Creatinine =< upper limit of normal (ULN) (Common Toxicity Criteria [CTC] grade 0) or calculated creatinine clearance (Jeliffe Formula) >= 60 ml/min
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limits of normal
• Bilirubin =< institutional upper limits of normal
• Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
• Patients must have met the pre-entry requirements
• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion criteria

• Patients with a concomitant malignancy other than non-melanoma skin cancer; with the exception of non-melanoma skin cancer, patients with a prior invasive malignancy who have been disease-free for < 5 years or who received prior chemotherapy for that malignancy
• Patients in whom pathological confirmation and estrogen receptor (ER)/progesterone receptor (PR) status of the tumor is not obtainable
• Patients for whom radiation therapy is planned during or after study chemotherapy prior to demonstrated progression
• Patients with concomitant medical illness such as serious uncontrolled infection, uncontrolled angina, or serious peripheral neuropathy, which, in the opinion of the treating physician, make the treatments prescribed on this study unreasonably hazardous for the patient
• Patients with third degree or complete heart block are not eligible unless a pacemaker is in place; patients on medications which alter cardiac conduction, such as digitalis, beta-blockers, or calcium channel blockers, or who have other conduction abnormalities or cardiac dysfunction may be placed on study at the discretion of the investigator
• Patients with history of myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure or symptoms suspicious for congestive heart failure are not eligible unless a left ventricular ejection fraction in the past 6 months is documented to be 50% or greater; patients who have had a left ventricular ejection fraction (LVEF) (performed for any reason) of less than 50% in the past 6 months are ineligible
• Patients whose circumstances will not permit study completion or adequate follow-up
• Patients who are sensitive to E. coli-derived drug preparations
• Patients with uterine carcinosarcoma or other non-epithelial uterine malignancies

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,381 participants in 2 patient groups

Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)

Active Comparator group

Description:

Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: Doxorubicin Hydrochloride

Other: Quality-of-Life Assessment

Biological: Pegfilgrastim

Biological: Filgrastim

Drug: Cisplatin

Drug: Paclitaxel

Other: Laboratory Biomarker Analysis

Arm II (paclitaxel, carboplatin)

Experimental group

Description:

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: Quality-of-Life Assessment

Drug: Carboplatin

Drug: Paclitaxel

Other: Laboratory Biomarker Analysis