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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-006312-38-HU
• Date of registration: 06/12/2010
• Prospective Registration: No
• Primary sponsor: SAKK (Swiss Group for Clinical Cancer Research)
• Public title: Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced, K-ras mutated rectal cancer. A randomized multicenter phase I/II trial.
• Scientific title: Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced, K-ras mutated rectal cancer. A randomized multicenter phase I/II trial.
• Date of first enrolment: 05/08/2009
• Target sample size: 47
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006312-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Hungary

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced K-ras mutated rectal cancer.

Intervention(s)

Trade Name: NEXAVAR
Product Name: NEXAVAR
Pharmaceutical Form: Film-coated tablet

Trade Name: Xeloda
Pharmaceutical Form: Film-coated tablet

Primary Outcome(s)

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.
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.

Primary end point(s): Phase I:
Dose limiting toxicity of the treatment combination sorafenib, capecitabine, and radiotherapy.
Phase IIa:
Pathological near complete or complete response (Dworak grade 3 and 4)

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.

Secondary ID(s)

SAKK 41/08