REDEL Trial: Reduced Elective Nodal Dose for Anal Cancer Toxicity Mitigation
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- University of Cincinnati
- Enrollment
- 33
- Locations
- 3
- Primary Endpoint
- Assess Toxicity Index for all GI, GU, Dermatologic, and Hematologic CTCAE events from treatment initiation through 90 days post treatment
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Reduced Elective Dose + Concurrent Capecitabine/Mitomycin C
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: Radiation (reduced elective nodal dose (30.6 Gy) (Radiation)
Reduced Elective Dose + Concurrent Capecitabine/Mitomycin C
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: Capecitabine (Drug)
Reduced Elective Dose + Concurrent Capecitabine/Mitomycin C
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: Mitomycin c (Drug)
Outcomes
Primary Outcomes
Assess Toxicity Index for all GI, GU, Dermatologic, and Hematologic CTCAE events from treatment initiation through 90 days post treatment
Time Frame: 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
Time Frame: 9 weeks post treatment
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 Outcomes
- Colostomy-Free-Survival - measured by follow up without colostomy(3 years (Patients followed 3 years post Treatment))
- Disease Free Survival measured by digital rectal exam(3 and 6 months post treatment)
- Local Regional Recurrence(6 months post treatment)
- Overall Survival - measured by survival or death at follow up(3 years (Patients followed 3 years post Treatment))
- Proportion of patients requiring a treatment break due to toxicity; measured by more than 3 consecutive fractions missed.(Measured during the 5.5 - 6 week treatment period)
Investigators
Jordan Kharofa
Principal Investigator
University of Cincinnati