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

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

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer; Cancer of Rectum; Cancer of the Rectum; Neoplasm, Rectum; Rectum Cancer; Rectum Neoplasms; Adenocarcinoma of the Rectum
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Radiation: Radiation

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU; 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

Drug: Oxaliplatin; Other Names: Eloxatin®; Drug: Leucovorin; Other Names: Wellcovorin; citrovorum factor; folinic acid; 5-formyl tetrahydrofolate; Drug: Fluorouracil; Other Names: 5-FU; 5-Fluorouracil; Radiation: Radiation

What is the study measuring?

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 ulcerNo radiographic evidence of tumor on DRESubstantial downsizing on MRINo suspicious mesorectal lymph nodes on MRINegative 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 imagingAny 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)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

General Publications

• Kim H, Pedersen K, Olsen JR, Mutch MG, Chin RI, Glasgow SC, Wise PE, Silviera ML, Tan BR, Wang-Gillam A, Lim KH, Suresh R, Amin M, Huang Y, Henke LE, Park H, Ciorba MA, Badiyan S, Parikh PJ, Roach MC, Hunt SR. Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. Clin Colorectal Cancer. 2021 Sep;20(3):e185-e193. doi: 10.1016/j.clcc.2021.03.003. Epub 2021 Apr 7.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2016
• Primary Completion (Actual): February 4, 2020
• Study Completion (Actual): March 29, 2020

Study Registration Dates

• First Submitted: December 23, 2015
• First Submitted That Met QC Criteria: December 23, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Neoplasms; Adenocarcinoma; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Levoleucovorin; Tetrahydrofolates; Formyltetrahydrofolates
• Other Study ID Numbers: 201512140

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No