Erlotinib in Combination With Cisplatin as Radiosensitizing Agents in Women Receiving Radiation Therapy for Locally Advanced Squamous Cell Carcinoma of the Cervix; A Phase I Trial
Erlotinib in Combination With Cisplatin as Radiosensitizing Agents in Women Receiving Radiation Therapy for Locally Advanced Squamous Cell Carcinoma of the Cervix; A Phase I Trial
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib and cisplatin may make tumor cells more sensitive to radiation therapy. Giving erlotinib together with cisplatin and radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given together with cisplatin and radiation therapy in treating patients with stage IB, stage II, stage III, or stage IVA cervical cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, open-label, dose-escalation study of erlotinib hydrochloride.
Patients receive oral erlotinib hydrochloride once daily on days 1-35 and cisplatin IV on days 1, 8, 15, 22, and 29. Patients also undergo radiotherapy daily, 5 days a week, for approximately 5 weeks concurrently with chemotherapy.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
After completion of study treatment, patients are followed at 6 weeks.
Inclusion Criteria:
Diagnosis of squamous cell carcinoma of the cervix
Scheduled to undergo standard radiotherapy and receive weekly cisplatin
ECOG performance status 0-2
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 1 week after completion of study treatment
Must be able to take oral medication
Exclusion Criteria:
Malabsorption syndrome
Serious underlying medical condition that would impair the ability of patient to receive treatment
Known hypersensitivity to erlotinib hydrochloride
Psychological, familial, sociological, or geographical conditions that would preclude study compliance
Less than 21 days since prior nonapproved or investigational drugs
Prior chemotherapy
Prior radiotherapy
Prior anti-epidermal growth factor receptor treatment
Prior gastrointestinal surgery that limits absorption (i.e., requiring total parenteral nutrition)
Concurrent use of any of the following agents and therapies: