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

Sponsored by:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00869570

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: sorafenib tosylate Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Radiation: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer Colorectal Cancer Radiation Therapy Surgery

Drug Information available for: Capecitabine Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Neoadjuvant Radiotherapy Combined With Capecitabine and Sorafenib in Patients With Advanced, K-Ras Mutated Rectal Cancer. A Multicenter Phase I/IIa Trial.

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Dose-limiting toxicity of the treatment combination (Phase I) [ Designated as safety issue: Yes ]
Pathological near complete or complete tumor response (Dworak grade 3 and 4) (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pathological response [ Designated as safety issue: No ]
R0 and R1 resection [ Designated as safety issue: No ]
Sphincter preservation [ Designated as safety issue: No ]
Downstaging of primary tumor and/or lymph nodes (comparison between mrT/N and ypT/N) [ Designated as safety issue: No ]
Postoperative complications within 8 weeks after surgery [ Designated as safety issue: No ]
Time to local relapse [ Designated as safety issue: No ]
Time to distant failure [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	47
Study Start Date:	March 2009

Detailed 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 twice 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869570

Locations

Switzerland
Kantonsspital Graubuenden	Recruiting
Chur, Switzerland, CH-7000
Contact: Roger von Moos, MD 41-81-256-6644 roger.vonmoos@ksgr.ch

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Principal Investigator:

Roger von Moos, MD

Kantonsspital Graubuenden

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000634955, SWS-SAKK-41/08, EudraCT-2008-006312-38, EU-20809
Study First Received:	March 25, 2009
Last Updated:	March 25, 2009
ClinicalTrials.gov Identifier:	NCT00869570 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the rectum
stage II rectal cancer
stage III rectal cancer

Study placed in the following topic categories:

Antimetabolites
Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Rectal Neoplasm
Intestinal Diseases
Protein Kinase Inhibitors

Rectal Diseases
Intestinal Neoplasms
Digestive System Diseases
Rectal Cancer
Gastrointestinal Neoplasms
Adenocarcinoma
Sorafenib
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Capecitabine
Antimetabolites, Antineoplastic
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Enzyme Inhibitors
Intestinal Diseases

Protein Kinase Inhibitors
Rectal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Gastrointestinal Neoplasms
Sorafenib
Colorectal Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009