This trial has been completed.

Condition colorectal cancer
Treatments capecitabine, sorafenib tosylate, radiation therapy
Phase phase 1/phase 2
Sponsor Swiss Group for Clinical Cancer Research
Start date March 2009
End date May 2013
Trial size 54 participants
Trial identifier NCT00869570, 2008-006312-38, CDR0000634955, SAKK 41/08, SWS-SAKK-41-08


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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
capecitabine XELODA
Phase II: 2 x 825 mg/m2 per day (during 5 weeks)
sorafenib tosylate BAY 43-9006
Phase II: 1 x 400 mg per day (during 5 weeks)
radiation therapy
Phase II: 1.8 Gy per day in 25 fractions (during 5 weeks)

Primary Outcomes

Dose-limiting toxicity of the treatment combination (Phase I)
time frame: during trial treatment (12 weeks)
Pathological near complete or complete tumor response (Dworak grade 3 and 4) (Phase II)
time frame: after trial treatment (approx. 12 weeks).

Secondary Outcomes

R0 and R1 resection
time frame: after trial treatment (approx. 12 weeks)
Postoperative complications
time frame: within 8 weeks after surgery
Time to distant failure
time frame: during 3 years follow-up.
Disease-free survival
time frame: during 3 years follow-up.
Adverse events as assessed by NCI CTCAE v3.0
time frame: during trial treatment.

Eligibility Criteria

Male or female participants from 18 years up to 120 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed locally advanced adenocarcinoma of the rectum (with or without nodal involvement) requiring surgery - Stage mrT3-4, and/or mrN1-2, M0 disease - Tumor with K-ras gene mutation as assessed locally - No distant metastases PATIENT CHARACTERISTICS: - WHO performance status 0-1 - Neutrophil count ≥ 1,500/mm^3 - Platelet count ≥ 100,000/mm^3 - Hemoglobin ≥ 10.0 g/dL - Creatinine clearance ≥ 50mL/min - AST ≤ 2.5 times upper limit of normal (ULN) - Total bilirubin ≤ 1.5 times ULN - PT/INR or PTT ≤ 1.5 times ULN - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective barrier contraception during and for 12 months after completion of study therapy - Is compliant and geographic proximity allows for proper staging and follow-up - No other malignancy within the past 5 years except adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer - No psychiatric disorder that would preclude understanding study-related information, giving informed consent, or complying with oral drug intake - No clinically significant (i.e., active) cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmia [even if controlled with medication]) or myocardial infarction within the past 12 months - No uncontrolled hypertension - No evidence or history of bleeding diathesis - No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome - No serious or underlying condition (e.g., active autoimmune disease, uncontrolled diabetes, or uncontrolled infection) that, in the judgement of the investigator, could preclude the ability of the patient to participate in the study - No known hypersensitivity to study drugs or to any other component of the study drugs PRIOR CONCURRENT THERAPY: - No prior treatment for rectal cancer - No prior organ allografts - More than 4 weeks since prior major surgery other than colostomy - More than 30 days since prior treatment in a clinical trial - No other concurrent experimental drugs or anticancer therapy - No concurrent brivudine, lamivudine, ribavirin, or any other nucleoside analogue - No concurrent drugs contraindicated for use with the study drugs - No other concurrent radiotherapy - No concurrent anticoagulation therapy other than low molecular weight heparin

Additional Information

Official title Neoadjuvant Radiotherapy Combined With Capecitabine and Sorafenib in Patients With Advanced, K-ras Mutated Rectal Cancer. A Multicenter Phase I/IIa Trial.
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Swiss Group for Clinical Cancer Research.