Recruiting
Phase 2

Pentoxifylline & α-Tocopherol

Sponsor:

University Health Network, Toronto

Code:

NCT06634056

Conditions

Non-Small Cell Lung Cancer

Radiation Induced Lung Injury (RILI)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pentoxifylline

Placebo

α-Tocopherol

Study Details

Brief summary:

Currently, the standard of care treatment for newly diagnosed, inoperable stage III non-small cell lung cancer is radiotherapy (RT) with concurrent chemotherapy, followed by immune checkpoint inhibitors (ICI). RT is a highly effect local treatment. However, high doses of radiation used in curative settings can cause adverse side effects. The most common RT side effect in lung cancer is Radiation Induced Lung Injury (RILI), which can manifest as pneumonitis and/or pulmonary fibrosis. Lung injury can negatively impact patients' well-being and quality of life, and may lead to increased mortality. Risk of lung injury is particularly increased when patients are treated with a combination of treatments (i.e., RT, chemotherapy, and ICI). The drug Pentoxifylline (in combination with α-Tocopherol (Vitamin E)) has been shown to prevent/alter the progression of lung injury and there is a growing body of evidence to support the safety and efficacy of phosphodiesterase inhibitors in cancer treatment. The proposed study aims to determine if the addition of Pentoxifylline, given in combination with α-Tocopherol (Vitamin E), to standard of care treatment will reduce side effects related to lung injury and improve quality of life in this study population.

Conditions

Non-Small Cell Lung Cancer

Radiation Induced Lung Injury (RILI)

Study ID

NCT06634056

Start date

Jun 15, 2026

Status verified date

Aug, 2026

Completion date

Nov 30, 2032

Anticipated

Primary completion date

Nov 30, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Female and/or male aged ≥ 18 years.
  • 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.
  • Adequate kidney function (Creatinine clearance > 50 mL/min) as per blood work done within 30 days of registration.

Exclusion Criteria:

  • Participation in another clinical study with an investigational product during the last 6 months prior to registration.
  • Patients who will have surgery as part of curative treatment.
  • Previous radiotherapy to intended treatment volumes in the thorax.
  • Active pregnancy.
  • Life expectancy of less than 12 months.
  • Hypersensitivity to Pentoxifylline or other xanthines such as caffeine, theophylline and theobromine or tocopherol (vitamin E).
  • Participant has a history of acute (within 3 months) myocardial infarction, coronary artery disease, or cardiac arrhythmias.
  • Ongoing hemorrhage or major bleeding risk. Patients on antiplatelets agents and anticoagulants (Aspirin, Clopidogrel, Ticlopidine, Cilostazol, Dipyridamole, Heparin, Dalteparin, Enoxaparin and Warfarin) can be enrolled, but major bleeding events will be captured. Patients on Warfarin will need frequent monitoring of their coagulation time to adjust Warfarin dosage.

Study Design

Enrollment

150 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Control Arm

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.

experimental: Experimental Arm

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.

Interventions

Pentoxifylline

Pentoxifylline 400 mg orally three times a day and α-Tocopherol IU orally two times a day on day one of radiotherapy and continue treatment for 6 months.

Placebo

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.

α-Tocopherol

Pentoxifylline 400 mg orally three times a day and α-Tocopherol IU orally two times a day on day one of radiotherapy and continue treatment for 6 months.

Primary outcome measure

  • Change in risk of Lung Injury [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Philip Wong MD

416-946-4501philip.wong4@uhn.ca

Locations

University Health Network - Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 2C1

Contacts

Philip Wong MD

416-946-4501philip.wong4@uhn.ca

Principal Investigator:

Philip Wong MD

More Information

Sponsor

University Health Network, Toronto

Last update posted

Aug 6, 2026

Last verified

Aug, 2026

Keywords

  • P4-PACIFIC
  • Radiation Induced Lung Injury (RILI)
  • Non-Small Cell Lung Cancer
  • Pentoxifylline
  • α-Tocopherol (Vitamin E)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University Health Network, Toronto on 2026-08-06.