Non-Operative Management and Early Response Assessment in Rectal Cancer

NCT03904043 | Completed Results DMC FDA Device

• 1 other identifier: 201904029
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 4

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.

Conditions

Adenocarcinoma of the Lower Rectum

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Progression-free Survival (PFS)

  At 2 years

• Incidence of Any Grade 3 or Higher Toxicity During Treatment

  From start of treatment through the completion of treatment (estimated to be 22 weeks)

• Incidence of Post Chemoradiotherapy Grade 3 or Higher Toxicity

  At 1 year after the start of radiation

• Quality of Anorectal Function as Measured by the FACT-C Questionnaire (Physical Well-Being)

  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)

  Baseline, Completion of chemo (up to 16 weeks), and 10-14 months after radiation therapy

Study Arms (2)

Radiation + FOLFOX

EXPERIMENTAL

* 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. Levoleucovorin may be substituted if leucovorin is not available. * 5-FU bolus day 1 every 14 days * 5-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; Drug: FOLFOX regimen

Radiation + CAPOX

EXPERIMENTAL

* 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 cycle * Oxaliplatin 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; Drug: CAPOX regimen

Interventions

Radiation therapy RADIATION

-Monday-Friday treatment is strongly recommended

Radiation + CAPOX; Radiation + FOLFOX

FOLFOX regimen DRUG

-CAPOX can be given as alternative

Radiation + FOLFOX

CAPOX regimen DRUG

Given as an alternative to FOLFOX

Radiation + CAPOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (4)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Related Links

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

MeSH Terms

Interventions

Radiotherapy; Folfox protocol; XELOX

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Dr. Michael Waters
• Organization: Washington University School of Medicine

m.r.waters@wustl.edu

314-747-7236

Study Officials

• Michael Waters, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 4, 2019
• Study Start: July 1, 2020
• Primary Completion: August 21, 2024
• Study Completion: January 25, 2026
• Last Updated: May 1, 2026
• Results First Posted: June 11, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

US (4)