A Phase I/II Study of Cisplatin and Radiation in Combination With Sorafenib in Cervical Cancer
This will be a multi-institution, single-arm, open-label, phase I/II trial. Eligible patients will have pathologically-proven T1b-3b, N0/1, M0 epithelial carcinoma of the cervix. We hypothesize that sorafenib in combination with chemotherapy and radiotherapy may have anti-tumor activity in patients with cervical cancer. Sorafenib has not previously been combined with conventional RT-CT to treat cervix cancer.
Cancer of the Cervix
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Cisplatin and Radiation in Combination With Sorafenib in Cervical Cancer|
- Determine the biologic activity of sorafenib in cervix cancer. [ Time Frame: Not Determined ] [ Designated as safety issue: Yes ]
- Determine the acute and late toxicity, and effect of sorafenib in combination with radiation and chemotherapy on the disease-free survival of patients with high-risk cervix cancer. [ Time Frame: Not Determined ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2007|
|Study Completion Date:||July 2015|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
|Experimental: Cisplatin and Radiation in Combination with Sorafenib||
200mg PO BID x 7 days prior to Radiation and Cisplatin for Low-Risk Patients or 200mg PO BID x 7 days prior to, and 35 days during Radiation and Cisplatin for High-Risk PatientsDrug: Cisplatin
40mg/m2 administered weekly via IV, with RadiationProcedure: Radiation
Administered for 30-40 days.Combination of external beam radiotherapy followed by intra-cavitary brachytherapy.
During the phase I component of the study, low risk patients (tumor size ≤5 cm and radiographically node negative) will receive sorafenib alone in escalating doses for at least 1 week prior to the start of conventional treatment with radiotherapy and chemotherapy (RT-CT). High risk patients (tumor > 5 cm or node positive) will receive sorafenib alone in escalating dose for at least 1 week prior to the start of RT-CT, as well as concurrently with RT-CT. Cohorts of 3 patients per dose level are planned. If 1/3 patients encounters a dose-limiting toxicity (DLT), then that cohort will be expanded to 6 patients. If >2/3 of patients encounter a DLT, then that dose level will be declared as the maximum tolerated dose (MTD). An additional 3 patients will be entered into the dose level one below the MTD. The recommended phase II dose (RPTD) is defined as the dose level with < 1/6 patients with DLT.
For the phase II component, all patients will receive sorafenib at the RPTD for at least 1 week prior to, and concurrent with, RT-CT.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00510250
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Amit Oza, MD FRCP||Princess Margaret Hospital, Canada|
|Principal Investigator:||Michael Milosevic, MD FRCPC||Princess Margaret Hospital, Canada|