RecruitingInterventionalPhase 1

Phase I Trial of Ultra-fractionated Adaptive Radiotherapy, Chemotherapy and Selective Omission of Surgery for Locally Advanced Rectal Cancer

NCT ID: NCT04677413Sponsor: University of Texas Southwestern Medical CenterLast updated: 2026-04-27

Summary

The rationale of this clinical trial is to assess the feasibility of selective non-operative management for locally advanced rectal cancer using dose-escalated ultra-fractionated short course radiation therapy interdigitated with chemotherapy. We believe delivering short course radiotherapy over a prolonged interval, at escalated doses and with concurrent chemotherapy may be feasible and allow for improved clinical response.

Detailed description

To determine the maximal tolerated dose (MTD) of dose-escalated hypofractionated adaptive RT, in patients with locally advanced rectal cancer treated with RT, FOLFOX (5-FU, oxaliplatin, leucovorin) or CAPOX (capecitabine, oxaliplatin) chemotherapy and selective omission of surgery.

Arms & interventions

RadiationUltrafractionated radiotherapy for rectal cancer
To determine the toxicity of dose-escalated hypofractionated RT, in patients with locally advanced rectal cancer treated with RT, FOLFOX or CAPOX chemotherapy and selective omission of surgery.

Outcome measures

Primary

To determine the maximal tolerated dose (MTD) of dose-escalated hypofractionated RT.
The MTD will be based upon toxicity, which will be assessed according to the NCI's CTCAE v5.0 toxicity criteria. Dose limiting toxicities will include any of the following Grade 3+ GI toxicities.
Time frame: 0 to 60 days post radiation therapy

Secondary

To evaluate the rate of clinical complete and near complete response to radiation and chemotherapy.
Time frame: 1 year
To determine the organ preservation rate at 1 year after radiotherapy and FOLFOX or CAPOX chemotherapy.
Time frame: 1 year
To evaluate local regional recurrence, defined as the time between date of therapy initiation and date of local progression.
Time frame: 1 year
To evaluate disease-free survival (DFS), defined as the time between date of therapy completion the first date of documented disease progression or death.
Time frame: 1 year
For patients undergoing surgery, to evaluate the rate of R0 resection, defined as a negative surgical margin at time of total mesorectal excision.
Time frame: 1 year
To evaluate the rate of distant failure, defined as development of disease outside of the pelvis.
Time frame: 1 year

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: 1. At least 18 years of age. Both men and women and members of all races and ethnic groups will be included. 2. Willing and able to provide written informed consent 3. Pathologic diagnosis of rectal adenocarcinoma 4. T3-4 and/or N+ disease per AJCC 8th edition 5. No prior treatment for rectal adenocarcinoma 6. Eastern Cooperative Group (ECOG) performance status of 0-2. 7. Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows: * WBC ≥ 3,000/mL; * ANC WBC ≥ 1,000/mL; * PLT ≥ 75,000/mL; * T Bili ≤ 1.5 x upper limit of normal (ULN); * AST/ALT ≤ 2.5 x ULN; * Creatinine not above ULN, or creatinine clearance \>50 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal. 8. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of study therapy through 90 days after the last dose of study drugs. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria: 1. Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT. 2. Prior RT to the pelvis. 3. Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements. 4. Psychiatric illness/social situations that would limit consenting and compliance with study requirements. 5. Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

Study locations (1)

UT Southwestern Medical Center

Dallas, Texas, 75390-8849

Recruiting

sarah Hardee · Contact

12146458525 sarah.neufeld@UTSouthwestern.edu

Nina Sanford, M.D. · Principal Investigator