Chemotherapy and Pelvic Radiation Therapy with or without Additional Chemotherapy in Treating Patients with High-Risk Early-Stage Cervical Cancer after Radical Hysterectomy

Summary

Objectives

PRIMARY OBJECTIVE:
I. To determine if adjuvant systemic chemotherapy following chemoradiation therapy will improve disease-free survival compared to chemoradiation therapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after a radical hysterectomy.

SECONDARY OBJECTIVES:
I. To evaluate adverse events.
II. To evaluate overall survival.
III. To evaluate quality of life.
IV. To evaluate chemotherapy-induced neuropathy.
V. To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy with respect to toxicity and local control.
VI. To collect fixed tissue to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival.
VII. To collect blood to identify secreted factors from serum and plasma that may be associated with adverse events or outcome, and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo standard external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin intravenously (IV) over 1 hour once weekly for 6 weeks.

NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy.

ARM II: Patients receive chemoradiotherapy as in Arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 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.