Pneumonitis Prevention Protocol Using Pentoxifylline and α-tocopherol In Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation

NCT06634056 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 24-5340
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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

Radiation Induced Lung Injury (RILI); Non-Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in risk of Lung Injury

  To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes the risk of lung injury within 12 months post radiotherapy. Lung injury as defined by Grade2+ pneumonitis.

  1 year

Secondary Outcomes (3)

• Change in Oncological Outcomes

  1 year

• Change in Grade 3-5 treatment related toxicities

  1 year

• Change in Quality of Life

  1 year

Study Arms (2)

Control Arm

PLACEBO COMPARATOR

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.

Other: Placebo

Experimental Arm

EXPERIMENTAL

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.

Drug: Pentoxifylline; Other: α-Tocopherol

Interventions

Pentoxifylline DRUG

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.

Experimental Arm

Placebo OTHER

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.

Control Arm

α-Tocopherol OTHER

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.

Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• AstraZeneca: collaborator

Study Sites (1)

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pentoxifylline; alpha-Tocopherol

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tocopherols; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Philip Wong MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 9, 2024
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): November 30, 2031
• Study Completion (Estimated): November 30, 2032
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

CA (1)