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

• ClinicalTrials.gov Identifier: NCT03904043
• Recruitment Status: Recruiting
• First Posted: April 4, 2019
• Last Update Posted: February 16, 2022
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Adenocarcinoma of the Lower Rectum	Radiation: Radiation therapy; Drug: FOLFOX regimen; Other: Functional Assessment of Cancer Therapy-Colorectal cancer (FACT-C) questionnaire; Procedure: Rectal biopsy samples; Procedure: Blood for ctDNA	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Non-Operative Management and Early Response Assessment in Rectal Cancer
• Actual Study Start Date: July 1, 2020
• Estimated Primary Completion Date: January 31, 2024
• Estimated Study Completion Date: July 31, 2025

Arms and Interventions

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 days Leucovorin day 1 every 14 days 5-FU bolus day 1 every 14 days 5-FU infusion day 1 every 14 days over 46 hours; Alternatively CAPOX (capecitabine and oxaliplatin) may be given for 5 cycles over 15 weeks.; 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; Other: Functional Assessment of Cancer Therapy-Colorectal cancer (FACT-C) questionnaire; -Baseline, completion of chemotherapy (3-8 weeks after the end of chemotherapy), and 10 to 14 months after radiotherapy; Procedure: Rectal biopsy samples; -Multiple biopsy samples of the rectal tumor will be taken from the patient tumor prior to treatment initiation for genomic extraction. For patients at affiliate sites who do not have enough tissue from the diagnostic biopsy, a repeat pre-treatment biopsy is optional.; Procedure: Blood for ctDNA; -Prior to the start of treatment, Post radiation therapy labs (with standard of care (SOC) CBC/CMP prior to start of cycle 1 of chemotherapy), Day 1 of cycle 2 of chemotherapy (with SOC CBC/CMP), Completion of chemotherapy (3-8 weeks after the end of chemotherapy), months 3, 6, 9, 12, 16, 20, 24 until salvage surgery or 2 years from completion of chemotherapy (whichever is first)

Outcome Measures

Primary Outcome Measures :

1. Clinical complete response rate [ Time Frame: Completion of treatment (estimated to be 22 weeks) ]

   -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)

Secondary Outcome Measures :

1. Progression-free survival (PFS) [ Time Frame: 2 years ]

   • Criteria for progressive disease

     *Increase in the size of primary tumor by RECIST criteria

   • New metastatic disease
2. Incidence of grade 3 or higher toxicity during treatment [ Time Frame: Completion of treatment (estimated to be 22 weeks) ]
   -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.
3. Incidence of post chemoradiotherapy grade 3 or higher toxicity [ Time Frame: 1 year ]
   -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.
4. Quality of anorectal function as measured by the FACT-C questionnaire [ Time Frame: 1 year (between 10-14 months post treatment start date) ]
   • Questionnaire with 5 sections (physical well-being, social/family well being, emotional well-being, functional well-being, and additional concerns)
   • 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 person has
5. Organ preservation rate [ Time Frame: 1 year ]
6. Organ preservation rate [ Time Frame: 2 years ]

Eligibility Criteria

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

Criteria

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 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.

Contacts and Locations

Contacts

Contact: Hyun Kim, M.D.; 314-362-8502; kim.hyun@wustl.edu

Locations

United States, Colorado

University of Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Jeffrey Olsen, M.D. 719-365-6800

Principal Investigator: Jeffrey Olsen, M.D.

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Christopher Hallemeier, M.D. hallemeier.christopher@mayo.edu

Principal Investigator: Christopher Hallemeier, M.D.

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Hyun Kim, M.D. 314-362-8502 kim.hyun@wustl.edu

Principal Investigator: Hyun Kim, M.D.

Sub-Investigator: Manik Amin, M.D.

Sub-Investigator: Sean Glasgow, M.D.

Sub-Investigator: Kian-Huat Lim, M.D., Ph.D.

Sub-Investigator: Haeseong Park, M.D.

Sub-Investigator: Matthew Mutch, M.D.

Sub-Investigator: Matthew Silviera, M.D.

Sub-Investigator: Rama Suresh, M.D.

Sub-Investigator: Benjamin R Tan, M.D.

Sub-Investigator: Nikolaos Trikalinos, M.D.

Sub-Investigator: Paul Wise, M.D.

Sub-Investigator: Yi Huang, M.S.

Sub-Investigator: David DeNardo, Ph.D.

Sub-Investigator: Radhika Smith, M.D.

Sub-Investigator: Lauren Henke, M.D.

Sub-Investigator: Shahed Badiyan, M.D.

Sub-Investigator: Pamela Samson, M.D.

Sub-Investigator: Carl DeSelm, M.D.

Sub-Investigator: Olivia Aranha, M.D., Ph.D.

United States, Vermont

University of Vermont Medical Center; Recruiting

Burlington, Vermont, United States, 05401

Contact: Chris Anker, M.D. 802-847-3506 chris.anker@uvmhealth.org

Principal Investigator: Chris Anker, M.D.

Sub-Investigator: Steven Ades, M.D.

Sub-Investigator: Maura Berry, M.D.

Sub-Investigator: Marc Greenblatt, M.D.

Sub-Investigator: Nataniel Lester-Coll, M.D.

Sub-Investigator: Peter Cataldo, M.D.

Sub-Investigator: Jesse Moore, M.D.

Sub-Investigator: Krista Evans, M.D.

Sponsors and Collaborators

Washington University School of Medicine

Investigators

• Principal Investigator: Hyun Kim, M.D.; Washington University School of Medicine

More Information

Additional Information:

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

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03904043
• Other Study ID Numbers: 201904029
• First Posted: April 4, 2019
• Last Update Posted: February 16, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Time Frame: Up to 5 years after completion of the study
• 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.

• 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

Additional relevant MeSH terms:

Adenocarcinoma; Rectal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases