Non-Operative Management and Early Response Assessment in Rectal Cancer (NOM-ERA)

The investigators' data from a phase I study of short course radiation therapy followed by chemotherapy showed 74% complete clinical response (cCR). Given the promising response rate, the investigators are evaluating short course radiation therapy (SCRT) followed by chemotherapy in a multi-institution phase II trial to validate the cCR rate of this treatment paradigm. SCRT has not been prospectively evaluated in non-operative management for patients with non-metastatic rectal adenocarcinoma.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Lower Rectum
• Intervention / Treatment: Radiation: Radiation therapy; Drug: FOLFOX regimen; Drug: CAPOX regimen

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-2a, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI
• Tumor ≤ 12 cm from anal verge as determined by MRI or endoscopy
• Clinically detectable (MR, endoscopy, or DRE) tumor present
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• At least 18 years of age

• Adequate bone marrow function defined as:

  • Absolute neutrophil count (ANC) > 1,500 cells/mm3
  • Hemoglobin> 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 Institutional Review Board (IRB)-approved written informed consent document.

Exclusion Criteria

• Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer.
• Prior oxaliplatin or capecitabine use for any malignancy
• No prior radiation therapy to the pelvis.
• A history of other malignancy (except non-melanomatous skin cancers) with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• Currently receiving any investigational agents.
• A history of allergic reaction attributed to compounds of similar chemical or biologic composition to capecitabine, 5FU, oxaliplatin, or leucovorin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to Department of Health and Human Services (DHHS) treatment guidelines is recommended. HIV testing for patients without a history of HIV is not a protocol requirement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation + FOLFOX; Pelvic radiotherapy 5GY x 5 fractions once daily; Radiation to extra-mesorectal node 7 Gy x 5 fractions once daily; FOLFOX should begin 2-4 weeks after completion of radiotherapy and will consist of FOLFOX x 8 cycles (16 weeks).Oxaliplatin day 1 every 14 daysLeucovorin day 1 every 14 days. Levoleucovorin may be substituted if leucovorin is not available.5-FU bolus day 1 every 14 days5-FU infusion day 1 every 14 days over 46 hours; An optional simultaneous integrated boost of 30 Gy in 5 fractions to the primary tumor is permitted	Radiation: Radiation therapy; -Monday-Friday treatment is strongly recommended; Drug: FOLFOX regimen; -CAPOX can be given as alternative
Experimental: Radiation + CAPOX; Pelvic radiotherapy 5GY x 5 fractions once daily; Radiation to extra-mesorectal node 7 Gy x 5 fractions once daily; CAPOX should begin 2-4 weeks after completion of radiotherapy and will consist of CAPOX x 5 cycles (15 weeks).Capecitabine 1000 mg/m^2 by mouth twice per day on days 1-14 of every 21 day cycleOxaliplatin 130 mg/m^2 intravenous on day 1 of each 21 day cycle; An optional simultaneous integrated boost of 30 Gy in 5 fractions to the primary tumor is permitted	Radiation: Radiation therapy; -Monday-Friday treatment is strongly recommended; Drug: CAPOX regimen; Given as an alternative to FOLFOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Complete Response Rate	- Criteria for clinical complete response: No residual gross tumor at procto/sigmoidoscopy; or only erythematous scar or ulcer; No palpable tumor on DRE; No radiographic evidence of tumor 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)	Completion of treatment (estimated to be 22 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Criteria for progressive disease:Increase in the size of primary tumor by RECIST criteria (increase of at least 20% from nadir in the sum of the target lesion, with an absolute increase of at least 5 mm)New metastatic disease; PFS is defined as the time from date of treatment to death or progression, which occurs first. The alive patients without progression are censored as the last date follow-up.	At 2 years
Incidence of Any Grade 3 or Higher Toxicity During Treatment	- 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 treatment through the completion of treatment (estimated to be 22 weeks)
Incidence of Post Chemoradiotherapy Grade 3 or Higher Toxicity	- 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.	At 1 year after the start of radiation
Organ Preservation Rate		At 1 year
Organ Preservation Rate		At 2 years
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (Physical Well-Being)	Physical Well-Being section of the FACT-C questionnaire consists of 7 questions.; Answers to the questions range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score for this section ranges from 0-28.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (Social/Family Well-Being)	Social/Family Well-Being section of the FACT-C questionnaire consists of 7 questions.; Answers to the questions range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score for this section ranges from 0-28.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (Emotional Well-Being)	Emotional Well-Being section of the FACT-C questionnaire consists of 6 questions.; Answers to the questions range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score for this section ranges from 0-24.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (Functional Well-Being)	Functional Well-Being section of the FACT-C questionnaire consists of 7 questions.; Answers to the questions range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score for this section ranges from 0-28.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (Colorectal Cancer Subscale)	Colorectal Cancer Subscale section of the FACT-C questionnaire consists of 7 scored questions.; Answers to the questions range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score for this section ranges from 0-28.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (FACT-G Total Score)	The FACT-G total score is calculated by adding the Physical Well Being subscale score, Social/Family Well Being subscale score, Emotional Well Being subscale score, and Functional Well Being subscale score; Answers to the questions comprising the subscales range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score ranges from 0-108.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (FACT-C-TOI Total Score)	The FACT-C-Trial Outcome Index (TOI) total score is calculated by adding the Physical Well Being subscale score, Functional Well Being subscale score, and the Colorectal Cancer subscale score; Answers to the questions comprising the subscales range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score ranges from 0-84.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy
Quality of Anorectal Function as Measured by the FACT-C Questionnaire (FACT-C Total Score)	The FACT-C total score is calculated by adding the Physical Well Being subscale score, Social/Family Well Being subscale score, Emotional Well Being subscale score, Functional Well Being subscale score, and the Colorectal Cancer subscale score; Answers to the questions comprising the subscales range from 0=not at all to 4=very much. The higher the total score the lower quality of life.; The total score ranges from 0-136.	Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Michael Waters, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

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): July 1, 2020
• Primary Completion (Actual): August 21, 2024
• Study Completion (Actual): January 25, 2026

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 3, 2019
• First Posted (Actual): April 4, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Rectal Neoplasms; Adenocarcinoma; Therapeutics; Radiotherapy; Folfox protocol; XELOX
• Other Study ID Numbers: 201904029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be shared with investigators who submit a sound proposal. Participants who opted out of data sharing in the informed consent will not be included.
• IPD Sharing Time Frame: Up to 5 years after completion of the study
• IPD Sharing Access Criteria: Proposals should be directed to kim.hyun@wustl.edu. To gain access, data requestors will need to sign a data access agreement and provide proof of appropriate regulatory approvals as necessary.

Drug and device information, study documents

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