Non-Small Cell Lung CancerPhase 2P4-PACIFICNCT06634056
Pneumonitis Prevention Protocol Using Pentoxifylline and α-tocopherol In Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation
A Phase 2 study testing Pentoxifylline and α-Tocopherol in people with Non-Small Cell Lung Cancer and Radiation Induced Lung Injury (RILI), run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, Radiation Induced Lung Injury (RILI)
- What is being tested?
- Pentoxifylline and α-Tocopherol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteCanada
- Study dates
- 15 Jun 2026to 30 Nov 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1
Philip Wong MD, 416-946-4501 ext. 6889, philip.wong4@uhn.ca
Philip Wong MD
About this study
Official title: Pneumonitis Prevention Protocol Using Pentoxifylline and α-tocopherol in Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation
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.
Read the 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).
- Being tested
- Pentoxifylline, Placebo, α-Tocopherol
- Keywords
- P4-PACIFIC, Radiation Induced Lung Injury (RILI), Non-Small Cell Lung Cancer, Pentoxifylline, α-Tocopherol (Vitamin E)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentoxifyllineDrug
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.
PlaceboOther
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-TocopherolOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Pentoxifylline; Other: α-Tocopherol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
Change in Oncological Outcomes
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes oncological outcomes of progression free survival and overall survival. Progression free survival as measured by RECIST 1.1.
Measured: 1 year
Change in Grade 3-5 treatment related toxicities
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes the incidence of Grade 3-5 treatment (chemoRT + ICI) related toxicity. Grade 3-5 treatment related toxicity measured as per CTCAE version 5.0.
Measured: 1 year
Change in Quality of Life
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes quality of life, as measured by FACT-LCS (version 4) scores
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2024
- Study start15 Jun 2026
- Primary completion30 Nov 2031 (estimated)
- Study completion30 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06634056
- Sponsor's protocol ID
- 24-5340
- Other IDs
- ESR-22-21739
- Acronym
- P4-PACIFIC
- Status last verified
- Aug 2026
- First submitted
- 7 Oct 2024
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pneumonitis Prevention Protocol Using Pentoxifylline and α-tocopherol in Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation
- ClinicalTrials.gov ID
- NCT06634056
- Acronym / sponsor ID
- P4-PACIFIC / 24-5340
- Keywords
- P4-PACIFIC, Radiation Induced Lung Injury (RILI), Non-Small Cell Lung Cancer, Pentoxifylline, α-Tocopherol (Vitamin E)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 15 Jun 2026 (actual)
- Primary completion
- 30 Nov 2031 (estimated)
- Study completion
- 30 Nov 2032 (estimated)
- First posted
- 9 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Arm | Placebo comparator | Other: PlaceboParticipants 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 Arm | Experimental | Drug: Pentoxifylline, Other: α-TocopherolParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PentoxifyllinePentoxifylline 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. | Drug | Experimental Arm |
| PlaceboOne 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 | Control Arm |
| α-TocopherolPentoxifylline 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. | Other | Experimental Arm |
Primary outcome
Change in risk of Lung Injury
Time frame: 1 year
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.
3 secondary outcomes
Change in Oncological Outcomes
Time frame: 1 year
Change in Grade 3-5 treatment related toxicities
Time frame: 1 year
Change in Quality of Life
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pentoxifylline and α-Tocopherol in people with Non-Small Cell Lung Cancer and Radiation Induced Lung Injury (RILI), run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Philip Wong MD (416-946-4501 ext. 6889, philip.wong4@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in risk of Lung Injury (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.