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)

Launched by M.D. ANDERSON CANCER CENTER · Jul 2, 2024

Keywords

ClinConnect Summary

The STOP4-LATE-FIBROSE trial is a study looking to find out if two medications, pentoxifylline with vitamin E or pravastatin, can help prevent or reduce lymphedema and fibrosis caused by radiation therapy in patients with certain types of throat cancer. Lymphedema is a condition where swelling occurs due to fluid buildup, and fibrosis is the thickening or scarring of tissue. This study is currently not recruiting participants, but it aims to include adults aged 18 and older who will receive radiation treatment for oropharyngeal squamous carcinoma.

To be eligible for this trial, participants must have a specific type of throat cancer and meet certain health criteria, such as having adequate kidney function and not having active liver disease. Participants will need to provide informed consent, meaning they agree to take part in the study after understanding what it involves. Throughout the trial, participants can expect regular check-ups and monitoring to ensure their safety and to track how well the medications work in preventing lymphedema and fibrosis. It’s important for potential participants, especially women, to discuss contraceptive options with their doctors, as the effects of these medications on pregnancy are not well known.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. T1-T4N0-3M0 oropharyngeal squamous carcinoma.
• • 2. Dispositioned to radiotherapy with prescribed dose to unilateral or bilateral neck(s).
• • 3. Creatinine clearance \>30mL/min
• • 4. 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
• • 5. ECOG performance status ≤2 (Karnofsky ≥60%,)
• • 6. 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 ≤ institutional ULN
• • 7. 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.
• • 8. 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.