Back to resultsREDEL Trial: Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation (REDEL)
Primary Purpose
Anal Cancer
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Radiation (reduced elective nodal dose (30.6 Gy)
Capecitabine
Mitomycin c
Sponsored by
About this trial
This is an interventional treatment trial for Anal Cancer focused on measuring Toxicity Mitigation, Reduced Elective Nodal Dose
Eligibility Criteria
Inclusion Criteria: Age ≥18 years. Patients must have stage T1-4N+M0 or T3/T4N0M0 locally advanced anal cancer as evidenced by a PET scan AND either a CT with contrast of the abdomen/pelvis or an MRI with contrast of the pelvis. All imaging must be from within 60 days prior to registration. Note: Patients with T2N0 disease will be allowed if the primary tumor is >4 cm. Patients with Stage I-T1N0M0 or Stage II-T2N0M0 (tumor ≤ 4cm) will be ineligible for participation. Patients with perianal cancer that is HPV associated (P16+) will be eligible if the tumor extends to the anal verge and the CTV will include the mesorectal, internal/external iliac, and inguinal lymph nodes. Patients with excision of the primary tumor but with node positive disease or residual disease at the primary if T3T4N0 will be eligible. ECOG performance status 0 or 1 (or Karnofsky ≥70, see Appendix A). Patients must be able to receive concurrent treatment with capecitabine and Mitomycin C in the opinion of the investigator. Creatinine Clearance must be > 30 ml/min. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Any prior pelvic radiation. History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine. Patients with uncontrolled intercurrent illness that in the opinion of the investigator would prevent receipt of radiation or capecitabine. a. Note: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Pregnant or breastfeeding women are excluded from this study. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the investigator. Patients with active autoimmune or connective tissue disease requiring systemic treatment are excluded from this study.
Sites / Locations
- University of Cincinnati Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Reduced Elective Dose + Concurrent Capecitabine/Mitomycin C
Arm Description
Reduced elective nodal dose (30.6 Gy); (28- 30 fractions given M-F for approximately 5.5 to 6 weeks) Capecitabine 825 mg/m2 BID on days with RT Mitomycin C 10 mg/m2 slow IV push Days 1 and 29
Outcomes
Primary Outcome Measures
Assess Toxicity Index for all GI, GU, Dermatologic, and Hematologic CTCAE events from treatment initiation through 90 days post treatment
Toxicity Index for all GI, GU, Dermatologic, and Hematologic CTCAE events from treatment initiation through 90 days post treatment. In patients treated with IMRT enrolled to NRG/RTOG 0529, the mean GI/GU/Derm/Hem TI was 3.858 (SD=0.892) assessed during this time period with standard nodal dose using a simultaneous integrated boost technique. Thirty-three patients will allow an effect size of 0.4 with 80% power and one-sided alpha of 0.05. This effect size is larger than the difference in toxicity observed compared to the historic standard of 3D-conformal radiation with IMRT (current standard) and thus felt to represent a clinically meaningful difference. The CTCAE Toxicity index will be determined for all Dermatologic, Gastrointestinal, Genitourinary, and hematologic events within 90 days from treatment initiation that are possible, probably, or definitely attributable to treatment.
Assess patient reported GI toxicity using PRO-CTCAE Diarrhea
PRO-CTCAE Diarrhea will be used to assess patient reported GI toxicity for the primary endpoint at weeks 3, 5, and 9 (approximately 1-month post-treatment). Any high grade PRO-CTCAE Diarrhea (frequently/almost constantly) in week 3-9 was reported in 71% of patients on a prior trial in this population (UC-GI-1601) with standard nodal dose. With n=33 at alpha =0.05 (actual alpha=0.033) and power=0.80, we can detect a reduction in the proportion of patients reporting any PRO-CTCAE high grade diarrhea (week 3, 5, 9) of at least 22.3%.
Secondary Outcome Measures
Colostomy-Free-Survival - measured by follow up without colostomy
Colostomy-Free-Survival - Time from treatment completion to any colostomy or last follow up without colostomy.
Disease Free Survival measured by digital rectal exam
Disease Free Survival - Failure to achieve complete response (CR) at 6 months or subsequent recurrence. There will be a documented clinical response assessment of the primary anal tumor primarily by using digital rectal exam at 3 and 6 months to define clinical complete response along with a review of imaging at 6 months. Any residual tumor at 6 months would be considered "failure to achieve a complete response" and would be considered a DFS event. Resolution of the primary tumor after chemoradiation and recurrence of tumor (any size) would be considered a DFS event. Persistence of disease in grossly enlarged lymph node (GTV Gross Nodes) at 6 months or resolution and then recurrence (any size) would be considered DFS event. New lesions in the elective nodal space or any other location will be considered a DFS event.
Local Regional Recurrence
Local Regional Recurrence - All failures within the PTVs for the primary tumor, for the involved Lymph Nodes, or for the Elective Lymph Nodes, including both patients who failed to achieve CR at 6 months and those occurring more than 6 months after completion of chemoradiation after initial CR.
Overall Survival - measured by survival or death at follow up
Overall Survival - Time from registration to death or last follow up
Proportion of patients requiring a treatment break due to toxicity; measured by more than 3 consecutive fractions missed.
Treatment breaks- The proportion of patients requiring a treatment break due to toxicity (more than 3 consecutive fractions missed) will be monitored and reported. In RTOG 0529, 50% of patients treated with standard nodal dose required a treatment break.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05902533
Brief Title
REDEL Trial: Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation
Acronym
REDEL
Official Title
REDEL Trial: Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 14, 2023 (Actual)
Primary Completion Date
August 14, 2026 (Anticipated)
Study Completion Date
August 14, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cincinnati
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To determine the efficacy of reduced elective nodal radiation in anal cancer patients undergoing chemoradiation in reducing toxicity compared to standard nodal irradiation.
Detailed Description
This is a multi-center, single arm prospective trial to evaluate whether reduced elective nodal dose (30.6 Gy) reduces toxicity as defined by the CTCAE Toxicity Index compared to historic patients treated with standard nodal dose on NRG/RTOG0529 and patient reported GI toxicity using the validated PRO-CTCAE scale for diarrhea compared to historic patients treated on UC-GI-1601.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anal Cancer
Keywords
Toxicity Mitigation, Reduced Elective Nodal Dose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Single arm prospective trial.
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Reduced Elective Dose + Concurrent Capecitabine/Mitomycin C
Arm Type
Experimental
Arm Description
Reduced elective nodal dose (30.6 Gy); (28- 30 fractions given M-F for approximately 5.5 to 6 weeks) Capecitabine 825 mg/m2 BID on days with RT Mitomycin C 10 mg/m2 slow IV push Days 1 and 29
Intervention Type
Radiation
Intervention Name(s)
Radiation (reduced elective nodal dose (30.6 Gy)
Intervention Description
28-30 fractions Monday through Friday of intended chemoradiation depending on the total dose required (50.4-54 Gy) which will occur over approximately 5.5 to 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
825 mg/m2 BID (Oral Twice daily on days with RT)
Intervention Type
Drug
Intervention Name(s)
Mitomycin c
Intervention Description
10 mg/m2 slow IV push Day 1 and 29
Primary Outcome Measure Information:
Title
Assess Toxicity Index for all GI, GU, Dermatologic, and Hematologic CTCAE events from treatment initiation through 90 days post treatment
Description
Toxicity Index for all GI, GU, Dermatologic, and Hematologic CTCAE events from treatment initiation through 90 days post treatment. In patients treated with IMRT enrolled to NRG/RTOG 0529, the mean GI/GU/Derm/Hem TI was 3.858 (SD=0.892) assessed during this time period with standard nodal dose using a simultaneous integrated boost technique. Thirty-three patients will allow an effect size of 0.4 with 80% power and one-sided alpha of 0.05. This effect size is larger than the difference in toxicity observed compared to the historic standard of 3D-conformal radiation with IMRT (current standard) and thus felt to represent a clinically meaningful difference. The CTCAE Toxicity index will be determined for all Dermatologic, Gastrointestinal, Genitourinary, and hematologic events within 90 days from treatment initiation that are possible, probably, or definitely attributable to treatment.
Time Frame
90 days post treatment
Title
Assess patient reported GI toxicity using PRO-CTCAE Diarrhea
Description
PRO-CTCAE Diarrhea will be used to assess patient reported GI toxicity for the primary endpoint at weeks 3, 5, and 9 (approximately 1-month post-treatment). Any high grade PRO-CTCAE Diarrhea (frequently/almost constantly) in week 3-9 was reported in 71% of patients on a prior trial in this population (UC-GI-1601) with standard nodal dose. With n=33 at alpha =0.05 (actual alpha=0.033) and power=0.80, we can detect a reduction in the proportion of patients reporting any PRO-CTCAE high grade diarrhea (week 3, 5, 9) of at least 22.3%.
Time Frame
9 weeks post treatment
Secondary Outcome Measure Information:
Title
Colostomy-Free-Survival - measured by follow up without colostomy
Description
Colostomy-Free-Survival - Time from treatment completion to any colostomy or last follow up without colostomy.
Time Frame
3 years (Patients followed 3 years post Treatment)
Title
Disease Free Survival measured by digital rectal exam
Description
Disease Free Survival - Failure to achieve complete response (CR) at 6 months or subsequent recurrence. There will be a documented clinical response assessment of the primary anal tumor primarily by using digital rectal exam at 3 and 6 months to define clinical complete response along with a review of imaging at 6 months. Any residual tumor at 6 months would be considered "failure to achieve a complete response" and would be considered a DFS event. Resolution of the primary tumor after chemoradiation and recurrence of tumor (any size) would be considered a DFS event. Persistence of disease in grossly enlarged lymph node (GTV Gross Nodes) at 6 months or resolution and then recurrence (any size) would be considered DFS event. New lesions in the elective nodal space or any other location will be considered a DFS event.
Time Frame
3 and 6 months post treatment
Title
Local Regional Recurrence
Description
Local Regional Recurrence - All failures within the PTVs for the primary tumor, for the involved Lymph Nodes, or for the Elective Lymph Nodes, including both patients who failed to achieve CR at 6 months and those occurring more than 6 months after completion of chemoradiation after initial CR.
Time Frame
6 months post treatment
Title
Overall Survival - measured by survival or death at follow up
Description
Overall Survival - Time from registration to death or last follow up
Time Frame
3 years (Patients followed 3 years post Treatment)
Title
Proportion of patients requiring a treatment break due to toxicity; measured by more than 3 consecutive fractions missed.
Description
Treatment breaks- The proportion of patients requiring a treatment break due to toxicity (more than 3 consecutive fractions missed) will be monitored and reported. In RTOG 0529, 50% of patients treated with standard nodal dose required a treatment break.
Time Frame
Measured during the 5.5 - 6 week treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years.
Patients must have stage T1-4N+M0 or T3/T4N0M0 locally advanced anal cancer as evidenced by a PET scan AND either a CT with contrast of the abdomen/pelvis or an MRI with contrast of the pelvis. All imaging must be from within 60 days prior to registration.
Note: Patients with T2N0 disease will be allowed if the primary tumor is >4 cm. Patients with Stage I-T1N0M0 or Stage II-T2N0M0 (tumor ≤ 4cm) will be ineligible for participation.
Patients with perianal cancer that is HPV associated (P16+) will be eligible if the tumor extends to the anal verge and the CTV will include the mesorectal, internal/external iliac, and inguinal lymph nodes.
Patients with excision of the primary tumor but with node positive disease or residual disease at the primary if T3T4N0 will be eligible.
ECOG performance status 0 or 1 (or Karnofsky ≥70, see Appendix A).
Patients must be able to receive concurrent treatment with capecitabine and Mitomycin C in the opinion of the investigator.
Creatinine Clearance must be > 30 ml/min.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Any prior pelvic radiation.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine.
Patients with uncontrolled intercurrent illness that in the opinion of the investigator would prevent receipt of radiation or capecitabine.
a. Note: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Pregnant or breastfeeding women are excluded from this study.
Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the investigator.
Patients with active autoimmune or connective tissue disease requiring systemic treatment are excluded from this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
UCCC Clinical Trials Office
Phone
513-584-7698
Email
cancer@uchealth.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jordan Kharofa, MD
Email
kharofjr@ucmail.uc.edu
Facility Information:
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Vollmer
Phone
513-213-3203
Email
mccordce@ucmail.uc.edu
First Name & Middle Initial & Last Name & Degree
Jordan Kharofa, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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REDEL Trial: Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation
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