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

Trial Summary

What is the purpose of this trial?

To learn if pentoxifylline and vitamin E or pravastatin can reduce radiation-induced lymphedema/fibrosis.

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.

What data supports the effectiveness of the drug Tocopherol + Pravastatin + Pentoxifylline for Radiation-Induced Lymphedema and Fibrosis?

Research shows that pravastatin, a component of the treatment, can reduce radiation-induced damage in normal tissues by decreasing inflammation and oxidative stress, which may help in conditions like radiation-induced lymphedema and fibrosis. ^{1 2 3 4 5}

Is the combination of Tocopherol, Pravastatin, and Pentoxifylline safe for humans?

Pravastatin has been used in clinical trials with over 15,000 patients and has shown a favorable safety profile, with common side effects including rash, gastrointestinal issues, and muscle pain. The combination of pravastatin and fenofibrate is generally well tolerated with few adverse effects. However, specific safety data for the combination of Tocopherol, Pravastatin, and Pentoxifylline is not provided in the available research. ^{1 3 5 6 7}

How does the drug combination of Tocopherol, Pravastatin, and Pentoxifylline differ from other treatments for radiation-induced lymphedema and fibrosis?

This drug combination is unique because it targets radiation-induced damage through multiple mechanisms: Pravastatin reduces inflammation and oxidative stress, Pentoxifylline improves blood flow and reduces fibrosis, and Tocopherol (a form of Vitamin E) acts as an antioxidant. Together, they may offer a comprehensive approach to mitigating radiation-induced tissue damage, which is not typically addressed by standard treatments. ^{4 5 8 9 10}

Research Team

Clifton D. Fuller

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

I am scheduled for radiotherapy targeting my neck.

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

Exclusion Criteria

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

Contraindications for MRI

I have a history of muscle disease or severe muscle breakdown.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term experience with pravastatin in clinical research trials. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pravastatin limits endothelial activation after irradiation and decreases the resulting inflammatory and thrombotic responses. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The effects of multiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3alpha-hydroxy isomeric metabolite. [2013]

4. Greece pubmed.ncbi.nlm.nih.gov

Pravastatin reduces radiation-induced damage in normal tissues. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pravastatin Attenuates Acute Radiation-Induced Enteropathy and Improves Epithelial Cell Function. [2020]

6. Spain pubmed.ncbi.nlm.nih.gov

[Combination of pravastatin and fenofibrate (Pravafenix ®). Safety studies]. [2014]

7. Japan pubmed.ncbi.nlm.nih.gov

Clinically Administered Doses of Pitavastatin and Rosuvastatin. [2021]

8. England pubmed.ncbi.nlm.nih.gov

DNA damage in cultured skin microvascular endothelial cells exposed to gamma rays and treated by the combination pentoxifylline and alpha-tocopherol. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of late administration of pentoxifylline and tocotrienols in an image-guided rat model of localized heart irradiation. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Striking regression of radiation-induced fibrosis by a combination of pentoxifylline and tocopherol. [2013]