Capecitabine and Radiation Therapy With or Without Panitumumab in Treating Patients With Advanced Rectal Cancer

NCT ID: NCT00814619

Last Updated: 2014-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2014-01-31

Brief Summary

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.

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

panitumumab

Intervention Type: BIOLOGICAL

Given IV

capecitabine

Intervention Type: DRUG

Given orally

therapeutic conventional surgery

Intervention Type: PROCEDURE

Patients undergo surgical resection

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Patients undergo radiotherapy

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.

Group Type: ACTIVE_COMPARATOR

capecitabine

Intervention Type: DRUG

Given orally

therapeutic conventional surgery

Intervention Type: PROCEDURE

Patients undergo surgical resection

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Patients undergo radiotherapy

Interventions

panitumumab

Given IV

Intervention Type: BIOLOGICAL

capecitabine

Given orally

Intervention Type: DRUG

therapeutic conventional surgery

Patients undergo surgical resection

Intervention Type: PROCEDURE

3-dimensional conformal radiation therapy

Patients undergo radiotherapy

Intervention Type: RADIATION

Other Intervention Names

Vectibix; Xeloda

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Helbling, MD

Role: STUDY_CHAIR

Onkozentrum Zürich

Locations

Szent Laszlo Korhaz

Budapest, , Hungary

Hirslanden Klinik Aarau

Aarau, , Switzerland

Kantonspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Saint Claraspital AG

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

OnkoZentrum Luzern at Klinik St. Anna

Lucerne, , Switzerland

Kantonsspital, Luzerne

Luzerne, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Hopital Regional de Sion-Herens-Conthey

Sion, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Onkozentrum

Zurich, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Hungary; Switzerland

References

Helbling D, Bodoky G, Gautschi O, Sun H, Bosman F, Gloor B, Burkhard R, Winterhalder R, Madlung A, Rauch D, Saletti P, Widmer L, Borner M, Baertschi D, Yan P, Benhattar J, Leibundgut EO, Bougel S, Koeberle D. Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07. Ann Oncol. 2013 Mar;24(3):718-25. doi: 10.1093/annonc/mds519. Epub 2012 Nov 8.

Reference Type: RESULT

PMID: 23139259 (View on PubMed)

Other Identifiers

SWS-SAKK-41-07

Identifier Type: -

Identifier Source: secondary_id

EudraCT-2008-006012-38

Identifier Type: -

Identifier Source: secondary_id

EU-20894

Identifier Type: -

Identifier Source: secondary_id

CDR0000629101

Identifier Type: -

Identifier Source: secondary_id

SAKK 41/07

Identifier Type: -

Identifier Source: org_study_id