Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum

Study Overview
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Brief Summary
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The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy.

Official Title
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Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum (NORMAL-R)

Conditions
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Rectal Cancer, Cancer of Rectum, Cancer of the Rectum, Neoplasm, Rectum, Rectum Cancer, Rectum Neoplasms, Adenocarcinoma of the Rectum

Intervention / Treatment
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* Radiation: Radiation
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-1, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI and/or endorectal ultrasound Tumor ≤ 12 cm from anal verge as determined by MRI or endoscopy a ECOG performance status 0-2 At least 18 years of age Adequate bone marrow function defined as: ANC > 1,500 cells/mm3 Hgb > 8 g/dl platelets >100,000 cells/mm3 Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Able to understand and willing to sign an IRB-approved written informed consent document. Exclusion Criteria: No clinically detectable (MR, endoscopy or DRE) tumor present Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer. Any evidence of disease from another malignancy or history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix). Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible. Currently receiving any investigational agents. A history of allergic reaction attributed to compounds of similar chemical or biologic composition to 5FU, oxaliplatin, or leucovorin. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry. Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

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: Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU<br>Radiotherapy will consist of five fractions, delivered once daily, to a total dose of 25Gy at 5 Gy per fraction. An optional concomitant boost may be delivered to the primary tumor of 1-2 Gy per day (30-35 Gy to tumor total). If a boost is given then the maximum allowed dose to small bowel is 25 Gy. Chemotherapy should begin two weeks (9-12 working days) after completion of radiotherapy. Oxaliplatin will be given intravenous (IV) over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. Leucovorin will be given IV over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. 5-FU bolus will given IV push on Day 1 every 14 days for a maximum of 8 cycles. 5-FU infusion will be given continuous IV on Day 1 over 46 hours every 14 days for a maximum of 8 cycles Alternatively, capecitabine/oxaliplatin (CAPE PO 1000 mg/m2 BID days 1-14 Q21 days, oxaliplatin IV 130 mg/m2 IV Q21 days on day 1) x 5 cycles over 15 weeks may be administered instead of FOLFOX | Radiation: Radiation<br> <br> Drug: Oxaliplatin<br> <br> * Other names: Eloxatin®;Drug: Leucovorin<br> <br> * Other names: 5-formyl tetrahydrofolate;Drug: Fluorouracil<br> <br> * Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Criteria for complete clinical response: No residual gross tumor at procto/sigmoidoscopy, or only erythematous scar or ulcer No radiographic evidence of tumor on DRE Substantial downsizing on MRI No suspicious mesorectal lymph nodes on MRI Negative biopsy from scar, ulcer, or former tumor site (if necessary according to surgeon's judgment) Criteria for no significant clinical response: Residual disease by DRE, endoscopy or MR. Increase in primary tumor size upon clinical exam or imaging Any new lesions | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire | -The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much). | Baseline | 
| Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire | -The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much). | Completion of chemoradiation (approximately 112 days) | 
| Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire | -The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much). | 10-14 months after chemoradiation (approximately 16-20 months) | 
| Number of Any Grade 3 or Higher Toxicities | -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. | From start of radiation treatment through 30 days after completion of treatment (approximately 18 weeks) | 
| Number of Post Chemotherapy Grade 3 or Higher Toxicities | -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. | Post-chemotherapy through 1 year follow-up (approximately 1 year and 4 months) | 
| Quality of Anorectal Function as Measured by the FACT-C Questionnaire | -The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much) | Baseline | 
| Quality of Anorectal Function as Measured by the FACT-C Questionnaire | -The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much) | Completion of chemoradiation (approximately 112 days) | 
| Quality of Anorectal Function as Measured by the FACT-C Questionnaire | -The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much) | 10-14 months after chemoradiation (approximately 16-20 months) |