Reversing radiotherapy-related fibrosis and lymphedema in head and neck cancer survivors

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

This trial will test whether adding one of several drugs (pravastatin, pentoxifylline, ketoprofen, or pirfenidone) to standard care can prevent or reduce radiation-related fibrosis and lymphedema in people treated for head and neck cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sex: Female
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06912763 on ClinicalTrials.gov

What this trial studies

This is a Bayesian adaptive, randomized platform trial that compares multiple candidate drugs against standard of care to find the most effective therapy for radiation-associated fibrosis and lymphedema after head and neck cancer treatment. Participants are head and neck cancer survivors with clinician-detected grade 2 or higher lymphedema/fibrosis at least six months after receiving ≥30 Gy radiation. Primary outcomes include clinician-rated CTC-AE fibrosis scores and specialist-rated HN-ELAF scores at 12 months, plus imaging-based endpoints such as swallowing dysfunction (DIGEST) and quantitative T1 MRI changes. The platform design allows adaptive allocation to favor better-performing agents over time and to efficiently estimate relative effect sizes between arms.

Who should consider this trial

Good fit: Ideal candidates are head and neck cancer survivors with no active disease who received ≥30 Gy to the neck and have measurable grade 2 or higher radiation-related lymphedema or fibrosis at least six months after radiotherapy and who meet safety criteria for the study drugs and MRI.

Not a fit: Patients with active liver disease, severe renal impairment, prior myopathy or rhabdomyolysis, diabetes, allergy to the study drugs, ongoing active cancer, or other contraindications to the interventions or imaging are unlikely to benefit or may be excluded.

Why it matters

Potential benefit: If successful, the trial could identify a drug that reduces or prevents progression of radiation-induced fibrosis and lymphedema, improving swallowing, neck function, and quality of life for survivors.

How similar studies have performed: Some individual antifibrotic or anti-inflammatory agents (for example pentoxifylline or pirfenidone) have shown promise in small studies for radiation fibrosis, but a randomized adaptive platform directly comparing multiple agents in head and neck survivors is novel.

Eligibility criteria

Eligibility Criteria Eligibility criteria (observational registry or randomization)

1. Prior history of head and neck cancer with no active disease.
2. Treated previously with radiotherapy with prescribed dose (greater or equal to 30Gy) to unilateral or bilateral neck(s)
3. Detectable CTC-AE G2+ lymphedema/fibrosis at \>6 months post-radiotherapy.
4. No active liver disease (Child-Pugh class B-C), cirrhosis, nor active alcoholism, nor history of ulcers.
5. No history of myopathy/rhabdomyolysis.
6. Creatinine clearance \<30mL/min.
7. No history of acute myocardial infarction or severe coronary disease.
8. Non-pregnant/post-menopausal, or male.
9. No history of diabetes mellitus
10. Allergy/hypersensitivity to HMG Co-A reductase inhibitor and/or xanthine derivatives, e.g., caffeine, theophylline, theobromine
11. No contraindications for magnetic resonance imaging a Subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional

Exclusion Criteria

1. Active liver disease (Child-Pugh class B-C), cirrhosis, nor active alcoholism.
2. History of myopathy/rhabdomyolysis.
3. History of acute myocardial infarction or severe coronary disease.
4. Pregnant/post-menopausal, or male.
5. History of diabetes mellitus.
6. Allergy/hypersensitivity to Hydroxymethylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor and/or xanthine derivatives, e.g., caffeine, theophylline, theobromine.
7. Contraindications for MRI Subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional
8. Participants who are receiving any other investigational agents.
9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to statins, hemorheologic agents or other agents used in study
10. Participants with psychiatric illness/social situations that would limit compliance with study requirements.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Clifton Fuller, MD — M.D. Anderson Cancer Center
• Study coordinator: Clifton Fuller, MD

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