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

NCT00814619 | Completed Phase 2

• 5 other identifiers: SAKK 41/07SWS-SAKK-41-07EudraCT-2008-006012-38EU-20894CDR0000629101
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 24

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Pathological complete or near-complete response (Dworak grade 3 and 4)

  after 13 weeks.

Secondary Outcomes (7)

• Pathological response

  after 13 weeks.

• R0 or R1 resection

  after 13 weeks.

• Postoperative complications (within 8 weeks after surgery)

  within 8 weeks after surgery

• Time to local relapse

  calculated from randomization to documented relapse or censored at the last CT and/or endorectal ultrasound without local relapse.

• Time to distant failure

  calculated from randomization to documented distant (metastatic) failure or censored at the last CT without distant (metastatic) failure.

Study Arms (2)

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.

Biological: panitumumab; Drug: capecitabine; Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy

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; Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy

Interventions

panitumumab BIOLOGICAL

Given IV

Also known as: Vectibix

Arm I

capecitabine DRUG

Given orally

Also known as: Xeloda

Arm I; Arm II

therapeutic conventional surgery PROCEDURE

Patients undergo surgical resection

Arm I; Arm II

3-dimensional conformal radiation therapy RADIATION

Patients undergo radiotherapy

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (24)

Szent Laszlo Korhaz

Budapest, 1097, Hungary

Location

Hirslanden Klinik Aarau

Aarau, CH-5001, Switzerland

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Saint Claraspital AG

Basel, CH-4016, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

OnkoZentrum Luzern at Klinik St. Anna

Lucerne, 6006, Switzerland

Location

Kantonsspital, Luzerne

Luzerne, CH-6000, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hopital Regional de Sion-Herens-Conthey

Sion, CH -1951, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

Onkozentrum

Zurich, 8038, Switzerland

Location

Klinik Hirslanden

Zurich, CH-8032, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 23139259 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; Capecitabine; Radiotherapy, Conformal

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Daniel Helbling, MD

  Onkozentrum Zürich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: December 25, 2008
• Study Start: November 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: January 1, 2014
• Last Updated: April 30, 2014

Record last verified: 2014-04

Locations

HU (1); CH (23)