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External-Beam Radiation Therapy, Capecitabine, and Sorafenib in Treating Patients With Locally Advanced Rectal Cancer

This study has been completed.
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research Identifier:
First received: March 25, 2009
Last updated: December 28, 2016
Last verified: December 2016

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.

Condition Intervention Phase
Colorectal Cancer
Drug: capecitabine
Drug: sorafenib tosylate
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Radiotherapy Combined With Capecitabine and Sorafenib in Patients With Advanced, K-ras Mutated Rectal Cancer. A Multicenter Phase I/IIa Trial.

Resource links provided by NLM:

Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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. ]

Enrollment: 54
Study Start Date: March 2009
Study Completion Date: September 2016
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Sorafenib & Capecitabine & RT

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
Drug: capecitabine
Phase II: 2 x 825 mg/m2 per day (during 5 weeks)
Other Name: XELODA
Drug: sorafenib tosylate
Phase II: 1 x 400 mg per day (during 5 weeks)
Other Name: BAY 43-9006
Radiation: radiation therapy
Phase II: 1.8 Gy per day in 25 fractions (during 5 weeks)

Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00869570

Szent Laszlo Korhaz
Budapest, Hungary, 1097
Saint Claraspital AG
Basel, Switzerland, CH-4016
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland, 6500
Inselspital, Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Hopital Cantonal Universitaire de Geneva HUG
Geneva, Switzerland, CH-1211
Kantonsspital Luzern
Luzern, Switzerland, 6000
OnkoZentrum Luzern at Klinik St. Anna
Luzern, Switzerland, 6006
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
SpitalSTS AG Simmental-Thun-Saanenland
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
Onkozentrum - Klinik im Park
Zurich, Switzerland, 8002
Onkozentrum Hirslanden
Zurich, Switzerland, CH-8008
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Stadtspital Triemli
Zürich, Switzerland, 8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Study Chair: Roger von Moos, MD Kantonsspital Graubuenden
  More Information

Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT00869570     History of Changes
Other Study ID Numbers: SAKK 41/08
2008-006312-38 ( EudraCT Number )
CDR0000634955 ( Other Identifier: )
Study First Received: March 25, 2009
Last Updated: December 28, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
adenocarcinoma of the rectum
stage II rectal cancer
stage III rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs processed this record on April 21, 2017