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

Phase 2

Not yet recruiting

• Conditions: Fibrosis Syndrome; Lymphedema; Head &Amp; Neck Cancer; Fibrosis
• Interventions: Drug: Pravastatin (drug); Drug: Pirfenidoneone; Drug: Pentoxifylline; Drug: ketoprofen; Other: Standard of Care (SOC); Drug: tocopherol

• Registration Number: NCT06912763
• Lead Sponsor: M.D. Anderson Cancer Center

Brief 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.

.

Study Timeline

• Study First Submitted: 2025-03-24
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-02
• Last Update Submitted: 2025-04-02
• Study First Posted: 2025-04-06
• Last Update Posted: 2025-04-06
• Study Start: 2025-09-18
• Primary Completion: 2031-03-01
• Study Completion: 2033-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 250

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment with Pravastatin QD	Pravastatin (drug)	40 mg/day for 12 months
Treatment with Pirfenidone TID	Pirfenidoneone	801 mg for 12 months
Treatment with Pentoxifylline TID + Tocopherol	Pentoxifylline	400 mg/1000 IU vitamin E for 12 months
Treatment with Ketoprofen TID	ketoprofen	75 mg for 12 months
Treatment with Pentoxifylline TID + Tocopherol	tocopherol	400 mg/1000 IU vitamin E for 12 months
Treatment with SoC (Control)	Standard of Care (SOC)	No pharmacologic intervention (control)

Primary Outcome Measures

Name	Time	Method
Safety and adverse events	Through study completion; an average of 1 year	Incidence of Adverse of Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events

Trial Locations

Locations (1)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States