Tocopherol + Pravastatin + Pentoxifylline for Radiation-Induced Lymphedema and Fibrosis

Overseen By Clifton Fuller, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents, Statins

Disqualifiers: Liver disease, Myopathy, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

295 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether certain medications, such as pentoxifylline (Trental), vitamin E, or pravastatin, can reduce swelling and tissue stiffness caused by radiation treatment. It targets individuals who have received radiation for oropharyngeal squamous carcinoma, a type of throat cancer. Participants will be divided into groups: one will take pravastatin, another will take pentoxifylline with vitamin E, and a control group will not receive any study drugs. Those who have undergone radiation therapy for throat cancer and meet criteria such as having no active liver disease might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking other investigational agents or have allergies to certain compounds used in the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using pentoxifylline and vitamin E together is safe and may help prevent some radiation side effects, such as tissue thickening (fibrosis). Studies have found that most people tolerate this treatment well, experiencing no significant side effects.

Research suggests that pravastatin can help protect against radiation damage. It has been used to treat radiation-related problems without causing major side effects for most people.

Both treatments have shown promise in reducing radiation-related issues, and research suggests they are safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for radiation-induced lymphedema and fibrosis, which often include therapies like manual lymphatic drainage and compression garments, this approach uses a combination of drugs to tackle the condition from the inside out. Pentoxifylline improves blood flow and reduces inflammation, pravastatin helps lower cholesterol and may have anti-inflammatory properties, and tocopherol, a form of vitamin E, acts as an antioxidant to protect cells. Researchers are excited about these treatments because they target the underlying causes of fibrosis and lymphedema, potentially offering a more comprehensive and effective solution than current external or supportive therapies.

What evidence suggests that this trial's treatments could be effective for radiation-induced lymphedema and fibrosis?

In this trial, participants will join different treatment groups to evaluate the effectiveness of various interventions for radiation-induced lymphedema and fibrosis. Research has shown that pravastatin, administered to Group 1, can help reduce radiation damage. It has effectively reduced scarring in patients receiving radiation treatment for head and neck cancer and may protect normal tissues from radiation effects.

Participants in Group 2 will receive a combination of pentoxifylline and tocopherol (vitamin E), which has been shown to reduce radiation-induced scarring. This combination is often used together and has proven effective in lowering the risk of some radiation side effects. Both treatments have shown promise in addressing problems caused by radiation therapy, such as swelling and scarring. ^{1 4 5 6 7}

Who Is on the Research Team?

Clifton D. Fuller

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals who have developed lymphedema or fibrosis as a result of radiation therapy. The specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and may be required to have a history of radiation treatment.

Inclusion Criteria

Creatinine clearance >30mL/min

My blood counts and liver/kidney functions are within normal ranges.

I am scheduled for radiotherapy targeting my neck.

Exclusion Criteria

Contraindications for MRI

Participants with psychiatric illness/social situations that would limit compliance with study requirements

I do not have severe liver disease, cirrhosis, or active alcoholism.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants begin treatment 6 months after radiation therapy, taking either pravastatin or pentoxifylline and vitamin E for about 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pentoxifylline
• Pravastatin
• Tocopherol

Trial Overview The study is testing whether pentoxifylline combined with vitamin E (tocopherol) or the drug pravastatin can help reduce symptoms of lymphedema and fibrosis caused by radiation. It's an interventional study where patients are likely randomly assigned to different treatments.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 2 Interventions

Beginning at 6 months after radiation therapy, participants will take pentoxifylline and vitamin E by mouth 3 times a day for about 12 months.

Group II: Group 1 Experimental Treatment 1 Intervention

Beginning at 6 months after radiation therapy, participants will take 40 mg pravastatin by mouth 1 time a day for about 12 months.

Group III: Group 3 Active Control 1 Intervention

Participants will not be given any of the study drugs, as this is the control group.

Pentoxifylline is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Trental for:

• Intermittent claudication

Approved in Canada as Trental for:

• Intermittent claudication

Approved in European Union as Trental for:

• Intermittent claudication

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Pravastatin has been shown to have a favorable safety profile in over 15,000 patients, with common withdrawal reasons being mild side effects like rash and gastrointestinal issues, but no significant adverse effects on eye health were noted.

The drug effectively lowers serum cholesterol levels regardless of patient demographics, and it is well tolerated when used in combination with other cholesterol-lowering therapies, indicating its potential for long-term use in preventing coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term experience with pravastatin in clinical research trials. McGovern, ME., Mellies, MJ.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19540105/

Pentoxifylline and vitamin E treatment for prevention of ... Conclusions: The combination of pentoxifylline and vitamin E was safe and may be used for the prevention of some radiation-induced side-effects. Publication ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0266435616306842

Use of pentoxifylline and tocopherol in radiation-induced ... Pentoxifylline and vitamin E are effective in reducing radiation-induced fibrosis, either individually or when combined (which is the most common approach).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00583700

Trental & Vitamin E for Radiation-Induced Fibrosis A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

4. nature.com nature.com/articles/s41598-024-57850-0

Evaluation of therapeutic use of a combination of ... Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness.

5. redjournal.org redjournal.org/article/S0360-3016(12)00870-X/abstract

Randomized Trial of Pentoxifylline and Vitamin E vs ... This study of postirradiation breast cancer patients treated with PTX/vitamin E or standard follow-up indicated a significant difference in radiation-induced ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29687536/

Pentoxifylline and vitamin E for treatment or prevention of ... The current review summarizes the use of pentoxifylline and vitamin E of treatment or prevention of radiation-induced fibrosis in breast cancer patients.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S095980490900375X

Pentoxifylline and vitamin E treatment for prevention of ... The combination of pentoxifylline and vitamin E was safe and may be used for the prevention of some radiation-induced side-effects.