Clinical trial NCT00814619: Capecitabine and Radiation Therapy With or Without Panitumumab in Treating Patients With Advanced Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
stage III rectal cancer
stage II rectal cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2008-12-25
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Pathological complete or near-complete response (Dworak grade 3 and 4)
timeFrame: after 13 weeks.
Secondary outcomes:
measure: Pathological response
timeFrame: after 13 weeks.
measure: R0 or R1 resection
timeFrame: after 13 weeks.
measure: Postoperative complications (within 8 weeks after surgery)
timeFrame: within 8 weeks after surgery
measure: Time to local relapse
timeFrame: calculated from randomization to documented relapse or censored at the last CT and/or endorectal ultrasound without local relapse.
measure: Time to distant failure
timeFrame: calculated from randomization to documented distant (metastatic) failure or censored at the last CT without distant (metastatic) failure.
measure: Disease-free survival
timeFrame: calculated from randomization to first relapse or death (whichever occurs first).
measure: Adverse events
timeFrame: All AEs will be assessed according to NCI CTCAE v3.0.
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Szent Laszlo Korhaz
city: Aarau
country: Switzerland
facility: Hirslanden Klinik Aarau
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Luzerne
country: Switzerland
facility: Kantonsspital, Luzerne
city: Luzern
country: Switzerland
facility: OnkoZentrum Luzern at Klinik St. Anna
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Sion
country: Switzerland
facility: Hopital Regional de Sion-Herens-Conthey
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Onkozentrum
city: Zurich
country: Switzerland
facility: Klinik Hirslanden
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Onkozentrum Zürich
name: Daniel Helbling, MD
role: STUDY_CHAIR
References:
citation: 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.