NCT06912763

Reversing External-beam Radiotherapy-associated Fibrosis Syndrome: an Interventional Bayesian Adaptive Randomized-controlled Orphan Drug Platform Trial for Orodental Sequelae (Reverse-fibrose)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: Female
• Age: —
• Healthy volunteers: Not accepted

Summary

To find out if adding medication can help treat or prevent lymphedema and/or fibrosis related to radiation therapy, in survivors of head and neck cancer. Researchers will compare these drugs to find the most effective therapy for preventing or limiting these side effects.

Detailed description

Primary Objectives 1. Determine the relative utility of candidate agents to reduce clinician-rated radiation lymphedema/fibrosis 1. Hyp 1: Participants receiving candidate agent(s) will exhibit a proportional lower rate of Common Toxicity Criteria- Adverse Event (CTC-AE v5.0) rating of Grade 2 or greater on either "Fibrosis deep connective tissue" or "Superficial soft tissue fibrosis" by formal clinician assessment at 12 months post-randomization. 2. Hyp 2: Participants receiving candidate agent(s) will exhibit a proportional lower rate of objective lymphedema/fibrosis rated as "moderate/severe" grade at any head and neck subsite as measured by the Head and Neck External Lymphedema and Fibrosis (HN-ELAF) Assessment Criteria by a certified lymphedema specialist at 12 months post-randomization. 2. Determine the relative effect size observed of candidate agent(s) to reduce objective imaging-derived measures of radiation lymphedema/fibrosis-related sequalae \[Primary\] 1. Hyp 3: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of objective DIGEST-detected swallowing dysfunction 12 months post-randomization. 2. Hyp 4: Participants receiving candidate agent(s) will exhibit a proportional lower rate of objective MRI-detected difference between 6- and 18-month post-randomization quantitative T1 (T1 mapping) intensity for paired muscle swallowing/neck/masticator muscles receiving \>=40Gy post-randomization. Secondary Objectives 1. Determine the relative effect size observed of candidate agent(s) to reduce patient reported measures of toxicity associated with lymphedema/fibrosis-related sequalae \[Secondary\] 1. Hyp 5: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of moderate-severe rated items "Fibrosis deep connective tissue" or "Superficial soft tissue fibrosis" by patient self-assessment using the Participant Reported Outcomes-CTCAE (PROCTCAE) Scale at 12-months post-randomization. 2. Hyp 6: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of moderate-severe rated symptom items by participant self-assessment using the Head and Neck External Lymphedema and Fibrosis (HN-ELAF) Symptom Inventory Scale at 12-months post-randomization. 3. Hyp 7: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of moderate-severe global symptom burden by participant self-assessment using the MD Anderson Symptom Inventory Scale at 12-months post-randomization. 4. Hyp 8: Participants receiving candidate agent(s) will exhibit a proportionally improved global quality of life as denoted by patient self-assessment using the EQ-5D Visual analogue Scale at 12-months post-randomization. .

Conditions

• Fibrosis Syndrome
• Lymphedema
• Head &Amp; Neck Cancer
• Fibrosis

Interventions

Type	Name	Description
DRUG	Pravastatin (drug)	Given PO
DRUG	Pentoxifylline	Given PO
DRUG	ketoprofen	Given PO
DRUG	Pirfenidoneone	Given PO
OTHER	Standard of Care (SOC)	SOC
DRUG	tocopherol	Given PO

Timeline

• Start date: 2025-08-08
• Primary completion: 2031-03-01
• Completion: 2033-03-01
• First posted: 2025-04-06
• Last updated: 2026-01-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study