Capecitabine, Irinotecan Hydrochloride, Cetuximab, and Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy, cetuximab, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase I/II trial is studying the side effects of giving capecitabine and irinotecan hydrochloride together with cetuximab and radiation therapy and to see how well it works in treating patients undergoing surgery for locally advanced rectal cancer.

Detailed Description
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OBJECTIVES: To assess the downstaging effectiveness and tolerability of neoadjuvant chemoradiotherapy comprising capecitabine, irinotecan hydrochloride, cetuximab, and radiotherapy in patients with locally advanced rectal cancer. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-6 and irinotecan hydrochloride IV over 1 hour once weekly in weeks 2-5. Patients also undergo pelvic radiotherapy once daily and receive oral capecitabine twice daily on days 1-5 in weeks 2-6. Patients undergo surgery 8 weeks after completion of chemoradiotherapy. After completion of study treatment, patients are followed up at 6, 12, 24, and 36 months. Peer Reviewed and Funded or Endorsed by Cancer Research United Kindom (UK).

Official Title
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EXCITE: Erbitux, Xeloda, Campto, Irradiation Then Excision for Locally Advanced Rectal Cancer (North West Clinical Oncology Group-04 on Behalf of the NCRI Rectal Cancer Subgroup)

Conditions
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Rectal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: capecitabine
* Drug: irinotecan hydrochloride
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the rectum MRI-defined locally advanced disease, as defined by 1 of the following: Mesorectal fascia involvement Mesorectal fascia threatened (tumor ≤ 1 mm from mesorectal fascia) Any T3 tumor < 5 cm from anal verge No evidence of metastatic disease PATIENT CHARACTERISTICS: ECOG or WHO performance status 0-1 ANC ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Serum bilirubin < 1.25 times upper limit of normal (ULN) Serum transaminase(s) < 3 times ULN Serum alkaline phosphatase < 5 times ULN Estimated glomerular filtration rate > 50 mL/min Not pregnant or nursing Fertile patients must use effective contraception Fit to receive all study treatments Able to comply with oral medication No comorbidity or coagulation problem that would deem the patient unsuitable for surgery No pre-existing condition that would preclude radiotherapy (e.g., fistulas, severe ulcerative colitis [particularly patients currently taking sulfasalazine], Crohn's disease, prior adhesions) No current or impending rectal obstruction (unless a defunctioning stoma is present) or metallic colonic rectal stent in situ No significant small bowel delineated within the radiotherapy fields No pelvic sepsis No gastrointestinal disorder that would interfere with oral therapy or oral bioavailability No uncontrolled cardiac, respiratory, or other disease that would preclude study therapy or informed consent No serious medical or psychiatric disorder that would preclude study therapy or informed consent No known dihydropyrimidine dehydrogenase deficiency PRIOR CONCURRENT THERAPY: No prior chemotherapy No prior radiotherapy to the pelvis No concurrent participation in other studies, except genetic studies (e.g., NSCCG-National Study of Colorectal Cancer Genetics) No concurrent St. John wort No other concurrent cytotoxic treatment or radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: capecitabine|nan|
|Drug: irinotecan hydrochloride|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: therapeutic conventional surgery|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologically confirmed R0 resection rate |  | Week 14 (6 weeks after treatment complete) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiotherapy compliance | Radiotherapy treatment and dosage is captured on weekly CRFs from week 2-6 | Weeks 2, 3, 4, 5 & 6 | 
| Grade 3 or 4 toxicity as assessed by NCI CTCAE v3.0 | Adverse events are recorded weekly on CRFs from week 1 of treatment until 4 weeks post treatment, then at 1 month post surgery and specified time points during long term follow up at 6, 12, 24 & 36 month intervals. | Baseline, week 1- 10, week 12 & 14 then at 6, 12, 24 & 36 months follow up | 
| Pathological complete response |  | Week 14 (surgery conducted 6 weeks from end of treatment) | 
| Post-operative morbidity |  | Week 14 | 
| Long-term morbidity |  | Week 14, then at 6, 12, 24 & 36 months follow up | 
| Disease-free survival |  | Baseline, week 1- 10, week 12, 14 & then at 6, 12, 24 & 36 months follow up | 
| Local failure-free survival |  | Baseline, weeks 1- 10, weeks 12 & 14 then at 6, 12, 24 & 36 months follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the rectum, Locally advanced rectal cancer