Know Cancer

forgot password

Neoadjuvant Radiotherapy Combined With Capecitabine and Sorafenib in Patients With Advanced, K-ras Mutated Rectal Cancer. A Multicenter Phase I/IIa Trial.

Phase 1/Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer

Thank you

Trial Information

Neoadjuvant Radiotherapy Combined With Capecitabine and Sorafenib in Patients With Advanced, K-ras Mutated Rectal Cancer. A Multicenter Phase I/IIa Trial.


- 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.

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity of the treatment combination (Phase I)

Outcome Time Frame:

during trial treatment (12 weeks)

Safety Issue:


Principal Investigator

Roger von Moos, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Kantonsspital Graubuenden


Switzerland: Swissmedic

Study ID:

SAKK 41/08



Start Date:

March 2009

Completion Date:

October 2016

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the rectum
  • stage II rectal cancer
  • stage III rectal cancer
  • Rectal Neoplasms
  • Colorectal Neoplasms