A Single Arm Trial of Oxaliplatin and 5FU With Concurrent Radiation in Patients With Metastatic Rectal Cancer

Study Overview
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Brief Summary
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This trial is a single-arm study for patients presenting with both local and metastatic adenocarcinoma of rectum. The aims of the trial are (1) to determine the tolerability rate, and (2) to determine toxicity rates, pelvic and distant response rates in patients with locally advanced rectal cancer in the presence of distant metastasis who are treated with an interdigitating chemotherapy (oxaliplatin/5-fluorouracil [5FU]) and radiotherapy regimen.

Detailed Description
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Week 1: Oxaliplatin 100 mg/m2 Day 1 (over 2 hours), leucovorin 200mg/m2 Day 1 concurrent with oxaliplatin over 2 hrs, then 5-FU 400mg/m2 bolus Day 1, then 5-FU continuous infusion 2.4 g/m2 over 46 hours from Day 1. Weeks 3 to 5: radiotherapy 25.2 Gy in 14 fractions over 3 weeks with 85 mg/m2 oxaliplatin on the first day and continuous infusion 5-FU 200 mg/m2/day on the days of radiotherapy, Week 6: as per Week 1, Weeks 8-10: as per Weeks 3-5 Weeks 11: as per Week 1.

Official Title
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A Single-Arm Prospective Trial Evaluating The Local And Systemic Benefits Of Oxaliplatin And 5FU With Concurrent Radiation In Patients With Metastatic Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: oxaliplatin
* Drug: fluorouracil
* Drug: leucovorin
* Procedure: External beam radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with previously untreated and pathologically proven adenocarcinoma of the rectum with distant metastasis who would benefit from combined local therapy and systemic chemotherapy. Lower border of tumour must be within 15cm of anal verge. Age >= 18 years. ECOG Performance Status 0-2 Absolute Neutrophil Count > 1.5x10^9/L, haemoglobin > 100 g/L, and platelets > 100x10^9/L. Renal: Creatinine clearance >= 55 mL/min (using radioisotope renal scan or derived from serum creatinine using the Cockcroft-Gault formula). Bilirubin <= 2.0 x upper limit of normal. ALT <= 5 x upper limit of normal Life expectancy in excess of 3 months. No symptomatic peripheral neuropathy > grade 2. Males or non-pregnant, non-lactating females. Female patients of child-bearing potential, not surgically sterilized, must use an adequate form of contraception (oral contraceptive pill or barrier method). Signed informed consent Exclusion Criteria: Prior pelvic radiotherapy Febrile intercurrent illness or infection. History of myocardial infarction within the previous six months or unstable cardiac disease or any other medical condition likely to compromise the safe delivery of chemotherapy or radiotherapy. Concurrent treatment with other anti-cancer therapy. Significant medical conditions which in the opinion of the investigator would compromise the planned delivery of the chemotherapy and radiotherapy or which may be potentially exacerbated by these modalities. Locally recurrent rectal cancer

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: oxaliplatin|Week 1: Oxaliplatin 100 mg/m2 Day 1 (over 2 hours), leucovorin 200mg/m2 Day 1 concurrent with oxaliplatin over 2 hrs (then 5-FU). Weeks 3 to 5: radiotherapy 25.2 Gy in 14 fractions over 3 weeks with 85 mg/m2 oxaliplatin on the first day Week 6: as per Week 1, Weeks 8-10: as per Weeks 3-5 Weeks 11: as per Week 1.|
|Drug: fluorouracil|Week 1: (after Oxaliplatin and leucovorin)5-FU 400mg/m2 bolus Day 1, then 5-FU continuous infusion 2.4 g/m2 over 46 hours from Day 1. Weeks 3 to 5: radiotherapy 25.2 Gy in 14 fractions over 3 weeks with 85 mg/m2 oxaliplatin on the first day and continuous infusion 5-FU 200 mg/m2/day on the days of radiotherapy, Week 6: as per Week 1, Weeks 8-10: as per Weeks 3-5 Weeks 11: as per Week 1.|
|Drug: leucovorin|Week 1: Oxaliplatin 100 mg/m2 Day 1 (over 2 hours), leucovorin 200mg/m2 Day 1 concurrent with oxaliplatin over 2 hrs (then 5-FU) Week 6: as per Week 1, Weeks 11: as per Week 1.|
|Procedure: External beam radiotherapy|Weeks 3 to 5: radiotherapy 25.2 Gy in 14 fractions over 3 weeks with 85 mg/m2 oxaliplatin on the first day and continuous infusion 5-FU 200 mg/m2/day on the days of radiotherapy, Weeks 8-10: as per Weeks 3-5|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability rate |  | as per protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity rates |  | as per protocol | 
| Pelvic response rate |  | as per protocol | 
| Distant response rate |  | as per protocol |