Pentoxifylline + Vitamin E for Non-Small Cell Lung Cancer

(P4-PACIFIC Trial)

Overseen By Philip Wong MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Pentoxifylline, Vitamin E

Disqualifiers: Pregnancy, Cardiac disease, Hemorrhage, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to reduce lung damage in individuals with stage III non-small cell lung cancer undergoing standard treatments like chemotherapy and radiotherapy. The study tests whether adding Pentoxifylline (Trental) and Vitamin E (α-Tocopherol) can lower the risk of radiation-induced lung injuries, which may cause serious breathing problems. Individuals diagnosed with stage III non-small cell lung cancer and scheduled for chemoradiation treatment might be suitable candidates for this trial. The trial includes two groups: one receiving the new treatment combination and another receiving a placebo. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on Warfarin, you will need frequent monitoring to adjust your dosage.

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

Research has shown that Pentoxifylline and Vitamin E are safe for people with cancer. Studies suggest these treatments might reduce the risk of serious lung issues after radiation therapy, such as lung inflammation (pneumonitis) and lung scarring (pulmonary fibrosis). One study found that patients taking these drugs during cancer treatment did not experience severe side effects from the drugs.

These results indicate that the treatment is generally well-tolerated. The current trial is in Phase 2, meaning the treatment has already demonstrated some safety in earlier studies. This phase focuses on testing the treatment's effectiveness and further confirming its safety in a larger group of people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about Pentoxifylline and Vitamin E (α-Tocopherol) for non-small cell lung cancer because they offer a fresh approach by potentially enhancing the effects of radiotherapy. Unlike typical chemotherapy or targeted therapies that directly attack cancer cells, Pentoxifylline improves blood flow and oxygenation, which may make cancer cells more susceptible to radiation. Meanwhile, Vitamin E acts as an antioxidant, which might protect healthy cells from radiation damage, potentially reducing side effects. This combination could lead to more effective and better-tolerated treatment options for patients.

What evidence suggests that Pentoxifylline and Vitamin E might be effective for reducing lung injury in non-small cell lung cancer?

This trial will compare the effects of Pentoxifylline combined with Vitamin E to a placebo in patients undergoing radiation therapy for non-small cell lung cancer. Studies have shown that taking Pentoxifylline with Vitamin E can help prevent or reduce lung injuries caused by radiation therapy in cancer treatment. Research indicates that this combination may lower the risk of severe lung inflammation, known as pneumonitis, which can occur after radiation. Pentoxifylline modestly enhances the effects of radiation therapy, potentially benefiting patients with non-small cell lung cancer. Additionally, these treatments are considered safe, and evidence suggests they might improve survival rates by reducing harmful side effects. Overall, this combination shows promise for better managing lung injury and improving quality of life during cancer treatment. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with stage III non-small cell lung cancer who can't have surgery and are about to start chemoradiation. They should not have had previous radiation therapy in the chest area or be taking other drugs that affect blood clotting.

Inclusion Criteria

* Histologically confirmed diagnosis of stage III NSCLC, planned for treatment with concurrent chemoradiation and consolidation immune checkpoint inhibitor as per standard of care with no medical contraindications to therapy.

* Patients with ECOG performance status 0-2 within 4 weeks of randomization.

* Adequate liver function (no evidence of Child-Pugh class C disease or cirrhosis) as per blood work done within 30 days of registration.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation Treatment

Participants receive concurrent chemoradiation therapy with either placebo or Pentoxifylline/α-Tocopherol starting on day one of radiotherapy

6 months

Regular visits as per standard chemoradiation protocol

Consolidation Therapy

Participants receive immune checkpoint inhibitor therapy as per standard of care following chemoradiation

6 months

Follow-up

Participants are monitored for safety, lung injury, oncological outcomes, and quality of life

12 months

Periodic visits for assessment

What Are the Treatments Tested in This Trial?

Interventions

• Pentoxifylline
• α-Tocopherol

Trial Overview

The study tests if Pentoxifylline combined with α-Tocopherol (Vitamin E) can prevent or lessen lung injury from radiation in patients undergoing standard chemoradiation treatment, compared to a placebo group.

How Is the Trial Designed?

Group I: Experimental Arm Experimental Treatment 2 Interventions

Participants in the experimental arm will start Pentoxifylline 400 mg orally three times a day and α-Tocopherol 400 IU orally two times a day on day one of radiotherapy and continue treatment for 6 months.

Group II: Control Arm Placebo Group 1 Intervention

Participants in the control arm will start one placebo orally three times a day and another placebo orally two times a day on day one of radiotherapy and continue treatment for 6 months.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study with Wistar albino rats, vitamin E supplementation after radiation exposure significantly reduced the development of pulmonary fibrosis compared to rats that received no treatment.

The combination of vitamin E and pentoxifylline showed even greater effectiveness in reducing fibrosis, although pentoxifylline alone did not demonstrate significant benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin E protects against the development of radiation-induced pulmonary fibrosis in rats. Bese, NS., Munzuroglu, F., Uslu, B., et al.[2013]

In a study of 66 patients with stage IIIB non-small cell lung cancer, those who received pentoxifylline (PTX) and alpha-tocopherol alongside radiotherapy had significantly better overall survival rates (55% at 1 year and 30% at 2 years) compared to the control group receiving only radiotherapy (40% at 1 year and 14% at 2 years).

The combination treatment also improved progression-free survival, with rates of 48% at 1 year and 23% at 2 years for the PTX and alpha-tocopherol group, compared to 24% and 18% in the control group, indicating a potential survival advantage from this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of concomitant use of pentoxifylline and alpha-tocopherol with radiotherapy on the clinical outcome of patients with stage IIIB non-small cell lung cancer: a randomized prospective clinical trial. Misirlioglu, CH., Erkal, H., Elgin, Y., et al.[2019]

In a phase II study involving 18 patients with grade three radiation-induced toxicity, the combination of pentoxifylline and tocopherol, along with inhaled carbogen, showed a 33% response rate in improving toxicity scores.

Patients receiving prolonged treatment (12 months) had a higher response rate compared to those on short treatment, with two patients achieving complete symptom resolution maintained for up to three years, suggesting prolonged therapy may be more beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized prospective study of extended tocopherol and pentoxifylline therapy, in addition to carbogen, in the treatment of radiation late effects. Brennan, S., Salib, O., O'Shea, C., et al.[2021]

In a case series of six patients with bisphosphonate-associated osteonecrosis (BON), treatment with pentoxifylline and α-tocopherol, alongside antimicrobial therapy, resulted in a significant 74% reduction in bony exposure and improved symptom control over an average follow-up of 10 months.

The findings suggest that pentoxifylline and α-tocopherol could be an effective management strategy for BON, indicating the need for further controlled trials to validate these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. Epstein, MS., Wicknick, FW., Epstein, JB., et al.[2013]

In a study of 91 lung cancer patients, the combination of pentoxifylline and vitamin E significantly reduced radiation-induced lung toxicity compared to a control group, particularly during the acute and subacute phases of treatment.

The treatment was well-tolerated and may be especially beneficial for patients undergoing concurrent chemo-radiotherapy or those with poor respiratory function, suggesting a potential strategy for minimizing side effects of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentoxifylline and alpha-tocopherol in prevention of radiation-induced lung toxicity in patients with lung cancer. Misirlioglu, CH., Demirkasimoglu, T., Kucukplakci, B., et al.[2019]

Citations

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withpower.com

withpower.com/trial/phase-2-pneumonia-10-2024-ed7c8

Pentoxifylline + Vitamin E for Non-Small Cell Lung Cancer

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Safety of Pentoxifylline and Vitamin E With Stereotactic Ablative Radiotherapy (SABR) in Non-small Cell Lung Cancers. ClinicalTrials.gov ID NCT01871454.