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

Trial Title: Pneumonitis Prevention Protocol Using Pentoxifylline and Α-tocopherol in Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation

NCT ID: NCT06634056

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

Conditions: Official terms:
Pneumonia
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Injury
Tocopherols
Vitamin E
Tocotrienols
alpha-Tocopherol
Pentoxifylline

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

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Intervention:

Intervention type: Drug
Intervention name: Pentoxifylline
Description: 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.
Arm group label: Experimental Arm

Intervention type: Other
Intervention name: Placebo
Description: 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.
Arm group label: Control Arm

Intervention type: Other
Intervention name: α-Tocopherol
Description: 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.
Arm group label: Experimental Arm

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.

Detailed description: This is a multi-centre, Phase II, double-blind, placebo-controlled randomized trial. Eligible participants will include newly diagnosed, inoperable Stage III patients with NSCLC who will be treated with radical intent concurrent chemoradiation therapy with planned consolidation immune checkpoint inhibitor (ICI) as per standard of care. Participants will be randomized in a 1:1 ratio between control arm (Placebos for 6 months) (Arm 1) and the experimental arm (Pentoxifylline/α-Tocopherol for 6 months) (Arm 2).

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University Health Network - Princess Margaret Cancer Centre

Address:
City: Toronto
Zip: M5G 2C1
Country: Canada

Contact:
Last name: Philip Wong MD

Phone: 416-946-4501

Phone ext: 6889
Email: philip.wong4@uhn.ca

Contact backup:
Last name: Philip Wong MD

Start date: November 30, 2024

Completion date: November 30, 2031

Lead sponsor:
Agency: University Health Network, Toronto
Agency class: Other

Collaborator:
Agency: AstraZeneca
Agency class: Industry

Source: University Health Network, Toronto

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06634056