Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

Study Overview
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Brief Summary
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To determine if short course radiotherapy followed by chemotherapy can maintain morbidity at or below levels reported with concurrent 5FU, oxaliplatin, and radiotherapy, while maintaining response rates comparable to what would be expected with radiotherapy and concurrent chemotherapy.

Detailed Description
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Our principal objectives in this trial will be to determine if short course radiotherapy followed by chemotherapy can maintain morbidity at or below levels reported with concurrent 5FU (oral capecitabine if 5FU is unavailable), oxaliplatin, and radiotherapy, while maintaining response rates comparable to what would be expected with radiotherapy and concurrent chemotherapy. If we can establish a T stage downstaging rate that is significantly better than 50% and if acute tolerance is acceptable, then we would consider this study as having provided sufficient pilot data to support including this approach as an arm in a multi-institution phase III trial. The long-term goal is improved overall control of disease by delivering better chemotherapy earlier.

Official Title
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A Phase II Evaluation of Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

Conditions
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Rectal Neoplasms

Intervention / Treatment
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* Radiation: External beam radiation
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: 5-FU
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven adenocarcinoma of the rectum Patient evaluated by surgeon and found to be a potential surgical candidate. Since the primary objectives are response to chemoradiation and acute toxicity, lesions which are initially unresectable are eligible-provided the surgeon feels that, if there is sufficient response, surgery could become feasible. Clinical evidence of T3 or T4 disease. This can be by imaging studies (see or by physical findings (tethering on palpation for T3 lesions or invasion of a neighboring organ for T4 lesions) Karnofsky Performance Status at >60 Laboratory criteria: Absolute neutrophil count >= 1.5 K Platelets >= 100 K Total Bilirubin <= 2.0; SGOT and Alkaline Phosphatase <= 2 x upper limit of normal Creatinine < 2.0 Hemoglobin >= 8.0 Informed consent signed Tumor measurable in at least one dimension. This may be, e.g. length and/or width measured endoscopically or on digital rectal examination, and maximum rectal wall thickness determined by imaging studies. Estimated longevity at least 12 months Patients with distant metastatic disease will be eligible if they satisfy all other conditions Exclusion Criteria: Pregnant women, children < 18 years, or patients unable to give informed consent Patients with a past history of pelvic radiotherapy. Patients with any other malignancy within the past 5 years except: skin cancer or in-situ cervical cancer Patients with known allergy/intolerance to 5FU, Leucovorin, Oxaliplatin, Capecitabine Prior chemotherapy for colorectal cancer. Grade >= 2 peripheral neuropathy Any condition which, in the opinion of the treating medical oncologist, renders the patient unfit for 5FU (oral capecitabine if 5FU is unavailable), Leucovorin, Oxaliplatin chemotherapy

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant radiation followed by FOLFOX<br>Radiation - 20 Gy in 5 fractions to regional nodes. 25 Gy in the same 5 fractions to macroscopic disease. This is given over 1 week. FOLFOX Chemotherapy - after two weeks rest - oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 IV/2 hours followed sequentially by 5FU 400 mg/m2 IV push and 5FU 2400 mg/m2 over 46 hour CIVI. Repeat ever other week for a total of 4 courses (this equals 6 weeks). If 5-FU is unavailable -- oral capecitabine can be given as 1000 mg/m2 BID on days 1-7 every 14 days. | Radiation: External beam radiation<br> <br> Drug: Oxaliplatin<br> <br> * Other names: Eloxatin;Drug: Leucovorin<br> <br> Drug: 5-FU<br> <br> * Other names: Efudex;Drug: Capecitabine<br> <br> * Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of T Stage Downstaging | T stage downstaging is defined as clinical pretreatment American Joint Committee on Cancer T stage (cT) being greater than pathologic T stage at surgery (ypT). | Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks) | 
| Preoperative Gastrointestinal Morbidity | As measured by participants who experience grade 3 or higher gastrointestinal morbidity | Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Any Late Grade 3 or Higher Morbidity |  | Preoperative (mean time from start of radiation to surgery 17.3 weeks (SD +/- 2.9 weeks) | 
| Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity |  | 1 year (completion of all treatment) | 
| Local Control | Kaplan-Meier projections Local control = control of primary tumor | 30 months | 
| Rate of Overall Control |  | 1 year | 
| Rate of Locoregional Control |  | 1 year | 
| Freedom From Disease Relapse | Kaplan-Meier projections. | 30 months | 
| Determine Quality of Anorectal Function | Anorectal function was measured by the participant's response to the FACT-C questionnaire question I have control of my bowels. The answers ranged from 0=not at all to 4=very much. | Up to 1 year |