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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00814619
First received: December 24, 2008
Last updated: April 29, 2014
Last verified: April 2014
  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
Biological: panitumumab
Drug: capecitabine
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Pathological complete or near-complete response (Dworak grade 3 and 4) [ Time Frame: after 13 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathological response [ Time Frame: after 13 weeks. ] [ Designated as safety issue: No ]
  • R0 or R1 resection [ Time Frame: after 13 weeks. ] [ Designated as safety issue: No ]
  • Postoperative complications (within 8 weeks after surgery) [ Time Frame: within 8 weeks after surgery ] [ Designated as safety issue: No ]
  • Time to local relapse [ Time Frame: calculated from randomization to documented relapse or censored at the last CT and/or endorectal ultrasound without local relapse. ] [ Designated as safety issue: No ]
  • Time to distant failure [ Time Frame: calculated from randomization to documented distant (metastatic) failure or censored at the last CT without distant (metastatic) failure. ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: calculated from randomization to first relapse or death (whichever occurs first). ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: All AEs will be assessed according to NCI CTCAE v3.0. ] [ Designated as safety issue: Yes ]

Enrollment: 68
Study Start Date: November 2008
Study Completion Date: January 2014
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: panitumumab
Given IV
Other Name: Vectibix
Drug: capecitabine
Given orally
Other Name: Xeloda
Procedure: therapeutic conventional surgery
Patients undergo surgical resection
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Active Comparator: 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.
Drug: capecitabine
Given orally
Other Name: Xeloda
Procedure: therapeutic conventional surgery
Patients undergo surgical resection
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Hungary
Szent Laszlo Korhaz
Budapest, Hungary, 1097
Switzerland
Kantonspital Aarau
Aarau, Switzerland, CH-5001
Hirslanden Klinik Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Saint Claraspital AG
Basel, Switzerland, CH-4016
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
OnkoZentrum Luzern at Klinik St. Anna
Luzern, Switzerland, 6006
Kantonsspital, Luzerne
Luzerne, Switzerland, CH-6000
Kantonsspital Olten
Olten, Switzerland, CH-4600
Hopital Regional de Sion-Herens-Conthey
Sion, Switzerland, CH -1951
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Regionalspital
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
City Hospital Triemli
Zurich, Switzerland, CH-8063
Klinik Hirslanden
Zurich, Switzerland, CH-8032
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Onkozentrum
Zurich, Switzerland, 8038
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Daniel Helbling, MD Onkozentrum Zürich
  More Information

Additional Information:
Publications:
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00814619     History of Changes
Other Study ID Numbers: SAKK 41/07, SWS-SAKK-41-07, EudraCT-2008-006012-38, EU-20894, CDR0000629101
Study First Received: December 24, 2008
Last Updated: April 29, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
adenocarcinoma of the rectum
stage III rectal cancer
stage II rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014