Prophylactic pravastatin versus pentoxifylline plus vitamin E to prevent radiation-related lymphedema and fibrosis

Systemic Therapy of Open-label Prophylactic Pravastatin or Pentoxifylline/Tocopherol Prevention of Lymphedema Advancing to Eventual Fibrosis: an Interventional Registry-embedded Bayesian Randomized Trial for Radiation Sequelae (STOP4-LATE-FIBROSE)

This trial will test whether taking pravastatin or taking pentoxifylline with vitamin E can reduce radiation-related lymphedema and fibrosis in adults receiving radiotherapy for oropharyngeal cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 295 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (other)
• Drugs / interventions: Radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06494111 on ClinicalTrials.gov

What this trial studies

This is an open-label, registry-embedded, Bayesian randomized Phase 2 trial at a single center comparing pravastatin to pentoxifylline plus tocopherol given prophylactically to adults undergoing radiotherapy for oropharyngeal squamous carcinoma. Participants are randomized to one of the active regimens and followed longitudinally during and after radiotherapy. Primary outcomes are clinician-rated measures of radiation-induced lymphedema and fibrosis, with secondary outcomes including imaging-derived objective measures and patient-reported toxicity and function. The design uses Bayesian methods embedded within a clinical registry to estimate relative effect sizes between the two interventions.

Who should consider this trial

Good fit: Adults (≥18 years) with untreated T0–T4 N0–3 M0 oropharyngeal squamous carcinoma who are planned for radiotherapy, have ECOG ≤2, adequate organ function, and creatinine clearance >30 mL/min are eligible.

Not a fit: Patients under 18, those with contraindications to pravastatin or pentoxifylline/tocopherol, pregnant women, or people with established severe lymphedema/fibrosis are unlikely to benefit from this preventive approach.

Why it matters

Potential benefit: If successful, one of these medications could lower the chance or severity of radiation-related lymphedema and fibrosis, improving function and quality of life for survivors.

How similar studies have performed: Small trials and observational studies have suggested pentoxifylline plus vitamin E can reduce radiation fibrosis in some settings, while pravastatin has more limited clinical data but preclinical evidence of anti-fibrotic effects.

Eligibility criteria

Inclusion Criteria:

• Untreated T0-T4N0-3M0 oropharyngeal squamous carcinoma.

1. Dispositioned to radiotherapy with prescribed dose to unilateral or bilateral neck(s).
2. Creatinine clearance \>30mL/min
3. Age ≥18 years. Because no dosing or adverse event data are currently available on the use of pentoxifylline/pravastatin in participants \<18 years of age, children are excluded from this study
4. ECOG performance status ≤2 (Karnofsky ≥60%,)
5. Participants must have adequate organ and marrow function as defined below

   * absolute neutrophil count ≥1,000/mcL
   * platelets ≥100,000/mcL
   * total bilirubin ≤ institutional upper limit of normal (ULN)
   * AST(SGOT)/ALT(SGPT) ≤3 x institutional ULN
   * creatinine ≤1.5 x institutional ULN
6. The effects of pentoxifylline/pravastatin on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following.

   * Postmenopausal (no menses in greater than or equal to 12 consecutive months).
   * History of hysterectomy or bilateral salpingo-oophorectomy.
   * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
   * History of bilateral tubal ligation or another surgical sterilization procedure.
   * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
7. Ability to understand and the willingness to sign a written informed consent document.

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

Conditions: Lymphedema, Fibrosis