Clinical trial NCT04677413: Ultra-fractionated Radiotherapy for Rectal Cancer
Official title: Phase I Trial of Ultra-fractionated Adaptive Radiotherapy, Chemotherapy and Selective Omission of Surgery for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Rectal Cancer
Keywords: Rectal Cancer,T3-4 or N+
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2020-12-21
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective dose evaluation
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the maximal tolerated dose (MTD) of dose-escalated hypofractionated RT.
timeFrame: 0 to 60 days post radiation therapy
Secondary outcomes:
measure: To evaluate the rate of clinical complete and near complete response to radiation and chemotherapy.
timeFrame: 1 year
measure: To determine the organ preservation rate at 1 year after radiotherapy and FOLFOX or CAPOX chemotherapy.
timeFrame: 1 year
measure: To evaluate local regional recurrence, defined as the time between date of therapy initiation and date of local progression.
timeFrame: 1 year
measure: To evaluate disease-free survival (DFS), defined as the time between date of therapy completion the first date of documented disease progression or death.
timeFrame: 1 year
measure: For patients undergoing surgery, to evaluate the rate of R0 resection, defined as a negative surgical margin at time of total mesorectal excision.
timeFrame: 1 year
measure: To evaluate the rate of distant failure, defined as development of disease outside of the pelvis.
timeFrame: 1 year
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT SOUTHWESTERN medical CENTRE
name: Nina Sanford, MD
role: PRINCIPAL_INVESTIGATOR
References: