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eoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced, K-ras mutated rectal cancer. A randomized multicenter phase I/II trial.

Conditions
Advanced K-ras mutated rectal cancer.
Registration Number
EUCTR2008-006312-38-HU
Lead Sponsor
SAKK (Swiss Group for Clinical Cancer Research)
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
47
Inclusion Criteria

- Histologically confirmed advanced adenocarcinoma of the rectum with or without nodal involvement requiring surgery, stage mrT 3/4 and/or mrN 1-2 cM0.
- Tumors with the K-ras gene mutation
- Patient is considered operable
- Age >= 18 years
- Adequate hematological values
- Adequate renal and hepatic function
- PT-INR <= 1.5 or PTT <= 1.5 x ULN
- Women are not breastfeeding, are using contraception if sexually active, are not pregnant
- Men agree not to father a child
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Previous malignancy within 5 years (with exception of adequately treated cervical carcinoma or localized non-melanoma skin cancer)
- Distant metastasis
- Concurrent treatment with other experimental drugs or other anti-cancer therapy
- Any prior treatment for rectal cancer
- Patients with evidence or history of bleeding diathesis
- Uncontrolled hypertension
- Organ allografts
- Any concomitant drugs contraindicated for use with the trial drugs

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Part I: to determine the recommended dose of the neoadjuvant regimen of capecitabine, sorafenib and external beam radiotherapy in patients with advanced K-ras mutated rectal cancer.<br>Part IIa: to assess the efficacy and safety of the neoadjuvant regimen of capecitabine, sorafenib and external beam radiotherapy in patients with advanced K-ras mutated rectal cancer.;Secondary Objective: Molecular correlates: to identify molecular biomarkers predictive for response to the neoadjuvant regimen of capecitabine, sorafenib and external beam radiotherapy and to test the performance of allele specific real time PCR for K-ras mutation screening and non-invasive follow-up in patients with advanced K-ras mutated rectal cancer.;Primary end point(s): Phase I:<br>Dose limiting toxicity of the treatment combination sorafenib, capecitabine, and radiotherapy.<br>Phase IIa:<br>Pathological near complete or complete response (Dworak grade 3 and 4)
Secondary Outcome Measures
NameTimeMethod
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