SABR + Pentoxifylline/Vitamin E for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Louisville

Disqualifiers: No prior thoracic radiotherapy, Pregnancy, Recent chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

59 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with lung cancer that has recurred or developed anew after previous radiation therapy. It combines a precise, high-dose radiation called Stereotactic Ablative Radiotherapy (SABR) with the drug pentoxifylline (Trental) and Vitamin E to evaluate their safety and effectiveness together. Suitable candidates have had lung cancer before, received radiation treatment, and now have a new or returning lung cancer near the same area. As a Phase 2 trial, this research focuses on measuring 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, but you cannot have had chemotherapy within 4 weeks before starting the trial, and you cannot have plans to take chemotherapy at the same time as the trial treatment.

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

Previous studies have shown that pentoxifylline, often combined with vitamin E, significantly protects against lung damage from radiation. This combination reportedly reduces radiation's harmful effects, easing the impact on normal tissues. It suggests that pentoxifylline, especially with vitamin E, is well-tolerated by patients undergoing treatments like SABR.

Research on stereotactic ablative radiotherapy (SABR) also shows it is safe. Studies indicate that patients did not experience severe long-term side effects after treatment, suggesting SABR is generally safe for treating lung cancer. Overall, both pentoxifylline with vitamin E and SABR have been found to be safe options, with no major safety concerns reported in the referenced studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Stereotactic Ablative Radiotherapy (SABR) with Pentoxifylline and Vitamin E for lung cancer because it offers a novel approach to treatment. Unlike the standard treatments like chemotherapy and traditional radiotherapy, this combination specifically aims to enhance the effectiveness of radiotherapy. Pentoxifylline, along with Vitamin E, may improve blood flow and protect normal tissues, potentially reducing side effects and improving the overall impact of the therapy. This strategy targets both the tumor directly and supports the surrounding tissue, which could lead to better outcomes for patients.

What evidence suggests that SABR and pentoxifylline could be effective for lung cancer?

This trial will evaluate the combination of Stereotactic Ablative Radiotherapy (SABR) with pentoxifylline and Vitamin E for treating non-small cell lung cancer. Studies have shown that pentoxifylline can enhance radiation therapy by altering its impact on cancer cells, potentially increasing treatment effectiveness. Pentoxifylline may also protect healthy lung tissue during radiation by reducing clotting and inflammation. SABR has improved overall survival in patients by targeting tumors more precisely than traditional methods. This combination aims to enhance treatment effectiveness while minimizing side effects. ^{2 5 6 7 8}

Who Is on the Research Team?

Neal E. Dunlap

Principal Investigator

James Graham Brown Cancer Center-U of Louisville

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a history of thoracic cancer treated previously, who now have new or recurrent lung malignancies. They should be in good physical condition (ECOG 0-1), not pregnant, willing to use birth control, and have had recent scans and pulmonary tests. Those with very poor lung function or recent chemotherapy are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

My lung cancer is newly diagnosed or has come back in the same area.

Imaging as follows: CT scan of the chest with IV contrast within 8 weeks of registration, Whole body PET scan within 8 weeks of registration, Pulmonary function test (PFTs), including diffusion capacity within 8 weeks of registration, Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential, Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control, Patients must provide study specific informed consent prior to study entry.

Exclusion Criteria

I haven't had chemotherapy in the last 4 weeks.

I have never had radiation therapy to my chest.

I will be receiving chemotherapy at the same time as radiotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic ablative radiotherapy (SABR) along with pentoxifylline and Vitamin E

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pentoxifylline
• Stereotactic Ablative Radiotherapy (SABR)

Trial Overview The study is examining the safety and effectiveness of combining Pentoxifylline medication with Stereotactic Ablative Radiotherapy (SABR) for treating new or returning lung cancers that were previously irradiated.

How Is the Trial Designed?

Group I: radiotherapy (SABR) plus pentoxifylline Experimental Treatment 2 Interventions

standard of care radiotherapy (SABR) plus pentoxifylline and Vitamin E

Pentoxifylline is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Trental for:

• Intermittent claudication

Approved in Canada as Trental for:

• Intermittent claudication

Approved in European Union as Trental for:

• Intermittent claudication

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

James Graham Brown Cancer Center

Collaborator

Trials

44

Recruited

9,200+

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]

The combination of pentoxifylline (PTX) and alpha-tocopherol (vitamin E) significantly reduces radiation-induced fibrosis (RIF) in breast cancer patients, achieving up to 68% regression in RIF surface area after a mean treatment duration of 24 months.

Shorter treatment durations (6-12 months) may lead to a rebound effect, with RIF surface area increasing by 40% after treatment discontinuation, suggesting that longer treatment (3 years or more) is necessary for severe cases to maintain benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis. Delanian, S., Porcher, R., Rudant, J., et al.[2017]

In a phase II trial involving 14 patients with brain metastases, the combination of pentoxifylline (PTX) and standard whole-brain radiation treatment (WBRT) showed a median survival time of 33 days, which aligns with historical control data.

The study indicated that PTX was well-tolerated, as toxicity was not a common reason for patients dropping out, suggesting that higher doses of PTX could be explored in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II evaluation of pentoxifylline combined with radiation in the treatment of brain metastases. Johnson, FE., Harrison, BR., McKirgan, LW., et al.[2013]

Stereotactic ablative radiation therapy (SABR) was found to be effective for treating pulmonary metastases, with a median follow-up of 23 months showing improved overall survival (OS) for patients with 3 or fewer metastases compared to those with more (74.2% vs. 59.3% at 24 months).

Patients with less responsive primary tumors (like adrenal or pancreatic cancers) had higher local failure rates, suggesting that higher doses of SABR or surgical options may be necessary for these cases to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. Pasalic, D., Lu, Y., Betancourt-Cuellar, SL., et al.[2021]

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]

The SABRTooth study aimed to assess the feasibility of a phase III randomized controlled trial comparing stereotactic ablative radiotherapy (SABR) to surgery for patients with stage I nonsmall cell lung cancer, but found that recruitment was challenging due to patients' treatment preferences.

Out of 318 patients considered, only 24 were randomized, with many preferring SABR over surgery, indicating that while SABR is a viable treatment option, more innovative study designs are needed to effectively evaluate its benefits compared to surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection. Franks, KN., McParland, L., Webster, J., et al.[2022]

Partial stereotactic ablative boost radiotherapy (P-SABR) for bulky non-small cell lung cancer (NSCLC) showed promising results, with a two-year local control rate of 85.7% and overall survival rate of 55.6% among 30 patients followed for a median of 10.3 months.

P-SABR was well tolerated, with no severe acute side effects observed, and it effectively increased the biological equivalent dose (BED) to the tumor while maintaining similar doses to surrounding organs-at-risk compared to conventional radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial stereotactic ablative boost radiotherapy in bulky non-small cell lung cancer: a retrospective study. Bai, Y., Gao, XS., Qin, SB., et al.[2022]

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 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]

Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC) and has shown benefits over lower-dose radiotherapy regimens.

While SABR is generally safe and cost-effective, it can lead to increased toxicity in patients with tumors near the tracheobronchial tree or those with interstitial lung disease, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy in lung cancer: an emerging standard. Mutsaers, A., Chen, H., Louie, AV.[2019]

In a study of 39 patients with 45 lung lesions treated with stereotactic ablative body radiotherapy (SBRT), local progression-free survival rates were high, with 90.5% at 1 year and 80.5% at 2 years, indicating effective tumor control.

The treatment was well-tolerated with only mild acute side effects, suggesting that the moderate dose schedules of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) are safe and effective for managing non-small cell lung cancer and metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. Duncker-Rohr, V., Nestle, U., Momm, F., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01871454

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

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10927136/

Effect of Pentoxifylline on Radiation Response of Non ... Conclusion: We concluded that Pento is a modestly effective radiation response modifier and provide benefit in the treatment of non-small cell lung cancer.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301603014445

Pentoxifylline in prevention of radiation-induced lung ... Pentoxifylline (Ptx) is thought to be helpful in preventing radiotoxicity by inhibiting platelet aggregation and tumor necrosis factor.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5601509/

A systematic review of outcomes following stereotactic ... As with other groups, the improvement in OS of patients with ES lung cancer compared with conventional fractionated RT puts forward the case for SABR as the ...

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02286-5

Comparison of outcome after stereotactic ablative ... This is the first study to evaluate the safety and efficacy of SABR for stage I metachronous NSCLC compared to primary lung cancer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/14697441/

Pentoxifylline in prevention of radiation-induced lung ... Conclusion: Our study showed a significant protective effect of Ptx for both early and late lung radiotoxicity. We recommend the prophylactic use of Ptx, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17873306/

Pentoxifylline and alpha-tocopherol in prevention of ... Combined use of pentoxifylline and vitamin E is reported to reduce radiation-induced toxicity in normal tissues at molecular level.

8. appliedradiationoncology.com appliedradiationoncology.com/articles/the-effect-of-pentoxifylline-and-vitamin-e-in-preventing-grade-3-radiation-pneumonitis-a-single-arm-phase-ii-prospective-study

The Effect of Pentoxifylline and Vitamin E in Preventing ... PTX and VE are safe interventions that may reduce rates of grade 3 pneumonitis for patients undergoing reirradiation for locoregionally ...