Non-Operative Management and Early Response Assessment in Rectal Cancer

Not Applicable

Active, not recruiting

• Conditions: Adenocarcinoma of the Lower Rectum
• Interventions: 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

• Registration Number: NCT03904043
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-03
• Study First Submitted QC: 2019-04-03
• Study First Posted: 2019-04-04
• Study Start: 2020-07-01
• Status Verified: 2024-08
• Primary Completion: 2024-08-21
• Last Update Submitted: 2024-08-22
• Last Update Posted: 2024-08-23
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 63

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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiation + FOLFOX	Radiation therapy	* 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 * 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 + FOLFOX	FOLFOX regimen	* 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 * 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 + FOLFOX	Functional Assessment of Cancer Therapy-Colorectal cancer (FACT-C) questionnaire	* 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 * 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 + FOLFOX	Rectal biopsy samples	* 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 * 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 + FOLFOX	Blood for ctDNA	* 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 * 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

Primary Outcome Measures

Name	Time	Method
Clinical complete response rate	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

Name	Time	Method
Incidence of grade 3 or higher toxicity during treatment	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.
Organ preservation rate	2 years
Progression-free survival (PFS)	2 years	* 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.
Incidence of post chemoradiotherapy grade 3 or higher toxicity	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.
Quality of anorectal function as measured by the FACT-C questionnaire	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

Trial Locations

Locations (4)

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States