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

Primary Purpose

Cancer of Rectum, Cancer of the Rectum, Neoplasm, Rectum

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Radiation
Oxaliplatin
Leucovorin
Fluorouracil
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer of Rectum

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).
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).
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).
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.
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.
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)
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)
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)

Full Information

First Posted
December 23, 2015
Last Updated
February 10, 2021
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02641691
Brief Title
Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum
Acronym
NORMAL-R
Official Title
Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum (NORMAL-R)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
May 27, 2016 (Actual)
Primary Completion Date
February 4, 2020 (Actual)
Study Completion Date
March 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer of Rectum, Cancer of the Rectum, Neoplasm, Rectum, Rectal Cancer, Rectum Cancer, Rectum Neoplasms, Adenocarcinoma of the Rectum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU
Arm Type
Experimental
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin®
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Wellcovorin, citrovorum factor, folinic acid, 5-formyl tetrahydrofolate
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
5-Fluorouracil, 5-FU
Primary Outcome Measure Information:
Title
Complete Response Rate
Description
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
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
Description
-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).
Time Frame
Baseline
Title
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
Description
-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).
Time Frame
Completion of chemoradiation (approximately 112 days)
Title
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
Description
-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).
Time Frame
10-14 months after chemoradiation (approximately 16-20 months)
Title
Number of Any Grade 3 or Higher Toxicities
Description
-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.
Time Frame
From start of radiation treatment through 30 days after completion of treatment (approximately 18 weeks)
Title
Number of Post Chemotherapy Grade 3 or Higher Toxicities
Description
-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.
Time Frame
Post-chemotherapy through 1 year follow-up (approximately 1 year and 4 months)
Title
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
Description
-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)
Time Frame
Baseline
Title
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
Description
-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)
Time Frame
Completion of chemoradiation (approximately 112 days)
Title
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
Description
-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)
Time Frame
10-14 months after chemoradiation (approximately 16-20 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hyun Kim, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34001462
Citation
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.
Results Reference
derived
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum

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