Back to resultsUltra-fractionated Radiotherapy for Rectal Cancer
Primary Purpose
Rectal Cancer
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ultrafractionated radiotherapy for rectal cancer
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal Cancer,T3-4 or N+
Eligibility Criteria
Inclusion Criteria:
- At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
- Willing and able to provide written informed consent
- Pathologic diagnosis of rectal adenocarcinoma
- T3-4 and/or N+ disease per AJCC 8th edition
- No prior treatment for rectal adenocarcinoma
- Eastern Cooperative Group (ECOG) performance status of 0-2.
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 m2 for participants with creatinine levels above institutional normal.
- 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:
- Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT.
- Prior RT to the pelvis.
- Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
- Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
- Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
Sites / Locations
- UT Southwestern Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Phase I Dose Cohorts
Arm Description
DOSE LEVEL 1 : 30 Gy (tumor)/ 25 Gy (pelvis) DOSE LEVEL 2 : 35 Gy (tumor)/ 25 Gy (pelvis) DOSE LEVEL 3 : 40 Gy (tumor)/ 25 Gy (pelvis)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
To evaluate the rate of clinical complete and near complete response to radiation and chemotherapy.
Clinical complete response, assessed at 4-8 weeks after completion of chemotherapy and radiation, will be defined based upon endoscopy and MRI as described in section 4.11.
To determine the organ preservation rate at 1 year after radiotherapy and FOLFOX or CAPOX chemotherapy.
Organ preservation rate will be defined as rate of intact rectum and no local regional failure at 1 year from completion of treatment.
To evaluate local regional recurrence, defined as the time between date of therapy initiation and date of local progression.
The rate of local regional recurrence will be defined as disease recurrence in the pelvis and will be recorded on a time interval since completion of treatment. This will be evaluated as a median and rate up to 1 year post treatment. The time will be backdated to when the recurrence was observed.
To evaluate disease-free survival (DFS), defined as the time between date of therapy completion the first date of documented disease progression or death.
The disease-free survival endpoint will be defined as the percent of patients without disease recurrence at 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.
R0 resection will be defined by the percent of patients with an R0 resection or negative surgical margin at the time of total mesorectal excision. Acute and late toxicities will be recorded as the rate of treatment related grade 3-5 adverse events experienced in the acute phase from initiation of therapy to 6 weeks treatment to the late phase 6 weeks to 1 year, using the NCI's CTCAE v5.0 toxicity criteria.
To evaluate the rate of distant failure, defined as development of disease outside of the pelvis.
The rate of distant failure will be recurrence of disease outside of the pelvis that will be collected on time interval since completion of therapy and be evaluated as a median or rate up to 1-year follow-up. Time will be backdated to when the recurrence was observed.
Full Information
NCT ID
NCT04677413
First Posted
December 16, 2020
Last Updated
November 30, 2022
Sponsor
University of Texas Southwestern Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04677413
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 3, 2021 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Rectal Cancer,T3-4 or N+
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Prospective dose evaluation
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase I Dose Cohorts
Arm Type
Experimental
Arm Description
DOSE LEVEL 1 : 30 Gy (tumor)/ 25 Gy (pelvis)
DOSE LEVEL 2 : 35 Gy (tumor)/ 25 Gy (pelvis)
DOSE LEVEL 3 : 40 Gy (tumor)/ 25 Gy (pelvis)
Intervention Type
Radiation
Intervention Name(s)
Ultrafractionated radiotherapy for rectal cancer
Intervention Description
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.
Primary Outcome Measure Information:
Title
To determine the maximal tolerated dose (MTD) of dose-escalated hypofractionated RT.
Description
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 Outcome Measure Information:
Title
To evaluate the rate of clinical complete and near complete response to radiation and chemotherapy.
Description
Clinical complete response, assessed at 4-8 weeks after completion of chemotherapy and radiation, will be defined based upon endoscopy and MRI as described in section 4.11.
Time Frame
1 year
Title
To determine the organ preservation rate at 1 year after radiotherapy and FOLFOX or CAPOX chemotherapy.
Description
Organ preservation rate will be defined as rate of intact rectum and no local regional failure at 1 year from completion of treatment.
Time Frame
1 year
Title
To evaluate local regional recurrence, defined as the time between date of therapy initiation and date of local progression.
Description
The rate of local regional recurrence will be defined as disease recurrence in the pelvis and will be recorded on a time interval since completion of treatment. This will be evaluated as a median and rate up to 1 year post treatment. The time will be backdated to when the recurrence was observed.
Time Frame
1 year
Title
To evaluate disease-free survival (DFS), defined as the time between date of therapy completion the first date of documented disease progression or death.
Description
The disease-free survival endpoint will be defined as the percent of patients without disease recurrence at 1-year.
Time Frame
1 year
Title
For patients undergoing surgery, to evaluate the rate of R0 resection, defined as a negative surgical margin at time of total mesorectal excision.
Description
R0 resection will be defined by the percent of patients with an R0 resection or negative surgical margin at the time of total mesorectal excision. Acute and late toxicities will be recorded as the rate of treatment related grade 3-5 adverse events experienced in the acute phase from initiation of therapy to 6 weeks treatment to the late phase 6 weeks to 1 year, using the NCI's CTCAE v5.0 toxicity criteria.
Time Frame
1 year
Title
To evaluate the rate of distant failure, defined as development of disease outside of the pelvis.
Description
The rate of distant failure will be recurrence of disease outside of the pelvis that will be collected on time interval since completion of therapy and be evaluated as a median or rate up to 1-year follow-up. Time will be backdated to when the recurrence was observed.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
Willing and able to provide written informed consent
Pathologic diagnosis of rectal adenocarcinoma
T3-4 and/or N+ disease per AJCC 8th edition
No prior treatment for rectal adenocarcinoma
Eastern Cooperative Group (ECOG) performance status of 0-2.
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 m2 for participants with creatinine levels above institutional normal.
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:
Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT.
Prior RT to the pelvis.
Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kimberly Zepeda
Phone
12146458525
Email
kimberly.zepeda@utsouthwestern.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Hardee
Phone
12146458525
Email
sarah.hardee@utsouthwestern.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nina Sanford, MD
Organizational Affiliation
UT SOUTHWESTERN medical CENTRE
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8849
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
sarah Hardee
Phone
214-645-8525
Email
sarah.neufeld@UTSouthwestern.edu
First Name & Middle Initial & Last Name & Degree
Nina Sanford, M.D.
12. IPD Sharing Statement
Learn more about this trial
Ultra-fractionated Radiotherapy for Rectal Cancer
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