Capecitabine and Radiation Therapy With or Without Panitumumab in Treating Patients With Advanced Rectal Cancer - Full Text View

Sponsored by:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00814619

Purpose

RATIONALE: 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. Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving capecitabine together with 3-D conformal radiation therapy is more effective with or without panitumumab in treating patients with advanced rectal cancer.

PURPOSE: This randomized phase II trial is studying giving capecitabine together with radiation therapy to see how well it works with or without panitumumab in treating patients with advanced rectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: panitumumab Procedure: 3-dimensional conformal radiation therapy Procedure: therapeutic conventional surgery	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Capecitabine Panitumumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Neoadjuvant Radiotherapy and Capecitabine With or Without Panitumumab in Patients With Advanced, K-Ras Unmutated Rectal Cancer. A Randomized Multicenter Phase II Trial

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

Primary Outcome Measures:

Pathological complete or near-complete response (Dworak grade 3 and 4) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pathological response [ Designated as safety issue: No ]
R0 or 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 [ Designated as safety issue: Yes ]

Estimated Enrollment:	67
Study Start Date:	November 2008

Arms	Assigned Interventions
Arm I: Experimental Patients receive panitumumab IV over 30-90 minutes on days 1, 15, 29, 43, and 57 and oral capecitabine twice daily on days 8-40. Beginning on day 8, patients undergo daily fractions of 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning approximately 6 weeks after completion of panitumumab and chemoradiotherapy, patients undergo surgery.	Drug: capecitabine Given orally Drug: panitumumab Given IV Procedure: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Procedure: therapeutic conventional surgery Patients undergo surgical resection
Arm II: Active Comparator Patients receive oral capecitabine twice daily on days 1-33. Patients undergo concurrent 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning 6 weeks after completion of chemoradiotherapy, patients undergo surgery.	Drug: capecitabine Given orally Procedure: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Procedure: therapeutic conventional surgery Patients undergo surgical resection

Detailed Description:

OBJECTIVES:

To assess the efficacy and safety of neoadjuvant capecitabine and concurrent 3-dimensional conformal radiotherapy with vs without panitumumab in patients with advanced K-ras unmutated rectal cancer.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, T stage (T3 vs T4), tumor localization measured from caudal part of the tumor to the anocutaneous line (< 10 cm vs ≥ 10 cm), and number of EGFR gene copies (< 2.9 vs ≥ 2.9). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive panitumumab IV over 30-90 minutes on days 1, 15, 29, 43, and 57 and oral capecitabine twice daily on days 8-40. Beginning on day 8, patients undergo daily fractions of 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning approximately 6 weeks after completion of panitumumab and chemoradiotherapy, patients undergo surgery.
Arm II: Patients receive oral capecitabine twice daily on days 1-33. Patients undergo concurrent 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning 6 weeks after completion of chemoradiotherapy, patients undergo surgery.

After completion of study therapy, patients are followed 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 advanced adenocarcinoma of the rectum with or without nodal involvement
- Stage mrT3-4 and/or mrN1-2, M0
- Tumors must express wild type K-ras gene
No distant metastasis

PATIENT CHARACTERISTICS:

WHO performance status 0-1
Able to undergo surgery
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 100 g/L
Creatinine clearance ≥ 50 mL/min
AST ≤ 2.5 times upper limit normal (ULN)
Total bilirubin ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must agree to use effective contraception during and for 12 months after completion of study
No malignancy within the past 5 years with the exception of 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 prior existing conditions that would preclude radiotherapy
No clinically significant (i.e., active) cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmia even if controlled with medication) or myocardial infarction within the past 12 months
No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
No serious underlying medical condition that, in the judgement of the investigator, could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
No known dihydropyrimidine dehydrogenase deficiency
No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

More than 30 days since prior treatment in a clinical trial
No other concurrent experimental drugs, anticancer therapy, or investigational treatments
No prior treatment for rectal cancer
No prior anti-EGFR antibody therapy (e.g., cetuximab) or small-molecule EGFR inhibitors (e.g., erlotinib hydrochloride)
No concurrent treatment with brivudine, lamivudine, ribavirin, or any other nucleoside analogues
No organ allografts
No concurrent drugs contraindicated for use with the trial drugs
No other concurrent anti-EGFR-targeting agents
No other concurrent radiotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814619

Locations

Switzerland
Swiss Group for Clinical Cancer Research	Recruiting
Zurich, Switzerland, 8038
Contact: Daniel Helbling, MD 41-43 344-3333

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Principal Investigator:

Daniel Helbling, MD

Onkozentrum

More Information

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

Study ID Numbers:	CDR0000629101, SWS-SAKK-41/07, EudraCT-2008-006012-38, EU-20894
Study First Received:	December 24, 2008
Last Updated:	December 24, 2008
ClinicalTrials.gov Identifier:	NCT00814619
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

Intestinal Neoplasms
Rectal neoplasm
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009