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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00869570
• Other study ID #: SAKK 41/08
• Secondary ID: SWS-SAKK-41-0820
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2009
• Est. completion date: September 2016

Study information

• Verified date: May 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: September 2016
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

Drug:
• capecitabine
Phase II: 2 x 825 mg/m2 per day (during 5 weeks)
• sorafenib tosylate
Phase II: 1 x 400 mg per day (during 5 weeks)

Radiation:
• radiation therapy
Phase II: 1.8 Gy per day in 25 fractions (during 5 weeks)

Locations

Country	Name	City	State
Hungary	Szent Laszlo Korhaz	Budapest
Switzerland	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	Luzern
Switzerland	OnkoZentrum Luzern at Klinik St. Anna	Luzern
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	SpitalSTS AG Simmental-Thun-Saanenland	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Onkozentrum - Klinik im Park	Zurich
Switzerland	Onkozentrum Hirslanden	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich
Switzerland	Stadtspital Triemli	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Hungary,  Switzerland, 

References & Publications (1)

von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bärtschi D, Zaugg K; Swiss Group for Clinical Cancer Research (SAKK). N — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity of the treatment combination (Phase I)		during trial treatment (12 weeks)
Primary	Pathological near complete or complete tumor response (Dworak grade 3 and 4) (Phase II)		after trial treatment (approx. 12 weeks).
Secondary	R0 and R1 resection		after trial treatment (approx. 12 weeks)
Secondary	Postoperative complications		within 8 weeks after surgery
Secondary	Time to distant failure		during 3 years follow-up.
Secondary	Disease-free survival		during 3 years follow-up.
Secondary	Adverse events as assessed by NCI CTCAE v3.0		during trial treatment.