External-Beam Radiation Therapy, Capecitabine, and Sorafenib in Treating Patients With Locally Advanced Rectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT00869570
- Lead Sponsor
- Swiss Group for Clinical Cancer Research
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving radiation therapy together with capecitabine and sorafenib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase I/II trial is studying the side effects and best dose of capecitabine when given together with sorafenib and external-beam radiation therapy and to see how well it works in treating patients with locally advanced rectal cancer.
- Detailed Description
OBJECTIVES:
* Determine the recommended dose of neoadjuvant capecitabine when given together with sorafenib tosylate and external-beam radiotherapy in patients with K-ras mutated, locally advanced rectal cancer. (Phase I)
* Assess the efficacy and safety of this regimen in these patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of capecitabine followed by a phase II study.
Patients receive oral capecitabine twice daily and oral sorafenib tosylate once daily on days 1-33. Patients also undergo external-beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Approximately 6 weeks after completion of neoadjuvant therapy, patients undergo surgery.
After completion of study therapy, patients are followed at 8 weeks and then periodically for up to 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm A: Sorafenib & Capecitabine & RT radiation therapy Sorafenib: day 1 to 33 (5 weeks, including Saturday and Sunday) every 24 hours, immediately or within two hours after RT according to the dose escalation table during phase I, and the recommended dose during phase IIa. The intake stops at the last day of RT. On nonradiotherapy days (e.g. Saturday, Sunday), the tablets have to be taken at the same time as during the week. * Capecitabine: day 1 to 33 (5 weeks, including Saturday and Sunday) according to dose escalation table during phase I, and at the recommended dose during phase IIa. The intake stops in the evening of the last day of RT. * External beam RT: Monday through Friday for 5 weeks starting on day 1 (daily fraction 1.8 Gy, final dose 45 Gy) each day at the same time (e.g. 11:00 a.m. daily). * Surgery: 6 weeks (± 1 week) after radiochemotherapy (RCT) has been completed Arm A: Sorafenib & Capecitabine & RT sorafenib tosylate Sorafenib: day 1 to 33 (5 weeks, including Saturday and Sunday) every 24 hours, immediately or within two hours after RT according to the dose escalation table during phase I, and the recommended dose during phase IIa. The intake stops at the last day of RT. On nonradiotherapy days (e.g. Saturday, Sunday), the tablets have to be taken at the same time as during the week. * Capecitabine: day 1 to 33 (5 weeks, including Saturday and Sunday) according to dose escalation table during phase I, and at the recommended dose during phase IIa. The intake stops in the evening of the last day of RT. * External beam RT: Monday through Friday for 5 weeks starting on day 1 (daily fraction 1.8 Gy, final dose 45 Gy) each day at the same time (e.g. 11:00 a.m. daily). * Surgery: 6 weeks (± 1 week) after radiochemotherapy (RCT) has been completed Arm A: Sorafenib & Capecitabine & RT capecitabine Sorafenib: day 1 to 33 (5 weeks, including Saturday and Sunday) every 24 hours, immediately or within two hours after RT according to the dose escalation table during phase I, and the recommended dose during phase IIa. The intake stops at the last day of RT. On nonradiotherapy days (e.g. Saturday, Sunday), the tablets have to be taken at the same time as during the week. * Capecitabine: day 1 to 33 (5 weeks, including Saturday and Sunday) according to dose escalation table during phase I, and at the recommended dose during phase IIa. The intake stops in the evening of the last day of RT. * External beam RT: Monday through Friday for 5 weeks starting on day 1 (daily fraction 1.8 Gy, final dose 45 Gy) each day at the same time (e.g. 11:00 a.m. daily). * Surgery: 6 weeks (± 1 week) after radiochemotherapy (RCT) has been completed
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity of the treatment combination (Phase I) during trial treatment (12 weeks) Pathological near complete or complete tumor response (Dworak grade 3 and 4) (Phase II) after trial treatment (approx. 12 weeks).
- Secondary Outcome Measures
Name Time Method R0 and R1 resection after trial treatment (approx. 12 weeks) Postoperative complications within 8 weeks after surgery Time to distant failure during 3 years follow-up. Adverse events as assessed by NCI CTCAE v3.0 during trial treatment. Disease-free survival during 3 years follow-up.
Trial Locations
- Locations (18)
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Kantonsspital - St. Gallen
🇨🇭St. Gallen, Switzerland
Onkozentrum - Klinik im Park
🇨🇭Zurich, Switzerland
Stadtspital Triemli
🇨🇭Zürich, Switzerland
Inselspital, Bern
🇨🇭Bern, Switzerland
Spitalzentrum Biel
🇨🇭Biel, Switzerland
Kantonsspital Luzern
🇨🇭Luzern, Switzerland
Saint Claraspital AG
🇨🇭Basel, Switzerland
Hopital Cantonal Universitaire de Geneva HUG
🇨🇭Geneva, Switzerland
UniversitaetsSpital Zuerich
🇨🇭Zurich, Switzerland
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
🇨🇭Bellinzona, Switzerland
Onkozentrum Hirslanden
🇨🇭Zurich, Switzerland
Szent Laszlo Korhaz
🇭🇺Budapest, Hungary
Universitaetsspital-Basel
🇨🇭Basel, Switzerland
Kantonsspital Bruderholz
🇨🇭Bruderholz, Switzerland
OnkoZentrum Luzern at Klinik St. Anna
🇨🇭Luzern, Switzerland
SpitalSTS AG Simmental-Thun-Saanenland
🇨🇭Thun, Switzerland