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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Phase II: 2 x 825 mg/m2 per day (during 5 weeks)
Phase II: 1 x 400 mg per day (during 5 weeks)
Phase II: 1.8 Gy per day in 25 fractions (during 5 weeks)
Szent Laszlo Korhaz
Budapest, Hungary
Saint Claraspital AG
Basel, Switzerland
Universitaetsspital-Basel
Basel, Switzerland
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland
Inselspital, Bern
Bern, Switzerland
Spitalzentrum Biel
Biel, Switzerland
Kantonsspital Bruderholz
Bruderholz, Switzerland
Kantonsspital Graubuenden
Chur, Switzerland
Hopital Cantonal Universitaire de Geneva HUG
Geneva, Switzerland
Kantonsspital Luzern
Lucerne, Switzerland
...and 8 more locations
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).
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.
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