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

Phase 2

Completed

• Conditions: Colorectal Cancer
• Interventions: Biological: panitumumab; Drug: capecitabine; Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy

• Registration Number: NCT00814619
• Lead Sponsor: Swiss Group for Clinical Cancer Research

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.

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2008-12-24
• Study First Submitted QC: 2008-12-24
• Study First Posted: 2008-12-25
• Primary Completion: 2010-05
• Study Completion: 2014-01
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-29
• Last Update Posted: 2014-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	capecitabine	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	therapeutic conventional surgery	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.
Arm I	therapeutic conventional surgery	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 I	panitumumab	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 I	3-dimensional conformal radiation therapy	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	3-dimensional conformal radiation therapy	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.
Arm II	capecitabine	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.

Primary Outcome Measures

Name	Time	Method
Pathological complete or near-complete response (Dworak grade 3 and 4)	after 13 weeks.

Secondary Outcome Measures

Name	Time	Method
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.
Adverse events	All AEs will be assessed according to NCI CTCAE v3.0.
Time to distant failure	calculated from randomization to documented distant (metastatic) failure or censored at the last CT without distant (metastatic) failure.
Pathological response	after 13 weeks.
Disease-free survival	calculated from randomization to first relapse or death (whichever occurs first).

Trial Locations

Locations (24)

Hirslanden Klinik Aarau; 🇨🇭 Aarau, Switzerland

City Hospital Triemli; 🇨🇭 Zurich, Switzerland

UniversitaetsSpital Zuerich; 🇨🇭 Zurich, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland

Kantonsspital - St. Gallen; 🇨🇭 St. Gallen, Switzerland

Klinik Hirslanden; 🇨🇭 Zurich, Switzerland

Saint Claraspital AG; 🇨🇭 Basel, Switzerland

Spitalzentrum Biel; 🇨🇭 Biel, Switzerland

Kantonsspital Bruderholz; 🇨🇭 Bruderholz, Switzerland

Szent Laszlo Korhaz; 🇭🇺 Budapest, Hungary

Kantonspital Aarau; 🇨🇭 Aarau, Switzerland

Kantonsspital Baden; 🇨🇭 Baden, Switzerland

Universitaetsspital-Basel; 🇨🇭 Basel, Switzerland

Istituto Oncologico della Svizzera Italiana; 🇨🇭 Bellinzona, Switzerland

Kantonsspital Graubuenden; 🇨🇭 Chur, Switzerland

Hopital Cantonal Universitaire de Geneve; 🇨🇭 Geneva, Switzerland

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Kantonsspital, Luzerne; 🇨🇭 Luzerne, Switzerland

OnkoZentrum Luzern at Klinik St. Anna; 🇨🇭 Luzern, Switzerland

Kantonsspital Olten; 🇨🇭 Olten, Switzerland

Hopital Regional de Sion-Herens-Conthey; 🇨🇭 Sion, Switzerland

Regionalspital; 🇨🇭 Thun, Switzerland

Kantonsspital Winterthur; 🇨🇭 Winterthur, Switzerland

Onkozentrum; 🇨🇭 Zurich, Switzerland