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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00814619
• Other study ID #: SAKK 41/07
• Secondary ID: SWS-SAKK-41-07Eu
• Status: Completed
• Phase: Phase 2
• First received: December 24, 2008
• Last updated: April 29, 2014
• Start date: November 2008
• Est. completion date: January 2014

Study information

• Verified date: April 2014
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 2014
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Biological:
• panitumumab
Given IV

Drug:
• capecitabine
Given orally

Procedure:
• therapeutic conventional surgery
Patients undergo surgical resection

Radiation:
• 3-dimensional conformal radiation therapy
Patients undergo radiotherapy

Locations

Country	Name	City	State
Hungary	Szent Laszlo Korhaz	Budapest
Switzerland	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	Luzern
Switzerland	Kantonsspital, Luzerne	Luzerne
Switzerland	Kantonsspital Olten	Olten
Switzerland	Hopital Regional de Sion-Herens-Conthey	Sion
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	City Hospital Triemli	Zurich
Switzerland	Klinik Hirslanden	Zurich
Switzerland	Onkozentrum	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Hungary,  Switzerland, 

References & 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete or near-complete response (Dworak grade 3 and 4)		after 13 weeks.	No
Secondary	Pathological response		after 13 weeks.	No
Secondary	R0 or R1 resection		after 13 weeks.	No
Secondary	Postoperative complications (within 8 weeks after surgery)		within 8 weeks after surgery	No
Secondary	Time to local relapse		calculated from randomization to documented relapse or censored at the last CT and/or endorectal ultrasound without local relapse.	No
Secondary	Time to distant failure		calculated from randomization to documented distant (metastatic) failure or censored at the last CT without distant (metastatic) failure.	No
Secondary	Disease-free survival		calculated from randomization to first relapse or death (whichever occurs first).	No
Secondary	Adverse events		All AEs will be assessed according to NCI CTCAE v3.0.	Yes