Papaverine + SBRT for Non-Small Cell Lung Cancer

Overseen By Miranda Bean

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: Pregnancy, Pneumonectomy, Hepatic insufficiency, others

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

Compensation: Varies

Number of Visits: 8

Duration: 2 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether combining papaverine hydrochloride with precise radiation therapy (SBRT, or Stereotactic Body Radiation Therapy) can effectively treat non-small cell lung cancer. Papaverine hydrochloride may increase cancer cells' sensitivity to radiation, potentially enhancing treatment success. The trial aims to confirm the safety and effectiveness of this approach for patients. Suitable candidates include those with non-small cell lung cancer who have a tumor smaller than 5 cm and have not undergone overlapping radiation treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must wait at least 2 weeks after your last dose of any prior chemotherapy, targeted therapy, or immunotherapy before starting the trial.

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

Research has shown that papaverine hydrochloride is under investigation for its potential to make tumors more responsive to radiation treatment, potentially improving treatment effectiveness, especially in difficult-to-treat areas. One study found that papaverine can make tumors with low oxygen levels more sensitive to radiation, enhancing its effectiveness. Although papaverine is usually well-tolerated, this trial is in an early stage, so researchers are still determining its safety and optimal dosage.

In contrast, stereotactic body radiation therapy (SBRT) has undergone more extensive study. Research has demonstrated that SBRT can be used safely and effectively for non-small cell lung cancer. It targets tumors precisely, helping to protect healthy tissue. Previous studies have shown that the side effects of this method are generally acceptable.

Overall, both papaverine and SBRT show promise in treating non-small cell lung cancer, but the safety of papaverine is still being carefully evaluated in early trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Papaverine Hydrochloride and Stereotactic Body Radiation Therapy (SBRT) for treating non-small cell lung cancer because it offers a unique approach by potentially enhancing the effectiveness of radiation therapy. Papaverine Hydrochloride is believed to improve blood flow to tumors, which may increase the oxygen levels and make cancer cells more susceptible to radiation damage. This combination could lead to more effective tumor control compared to standard treatments like chemotherapy or traditional radiation therapy. Additionally, the precise delivery of SBRT allows for high doses of radiation in fewer sessions, possibly reducing treatment times and side effects.

What evidence suggests that papaverine hydrochloride and SBRT might be an effective treatment for non-small cell lung cancer?

Research has shown that papaverine hydrochloride can make tumor cells more sensitive to radiation therapy by increasing oxygen levels in tumors, enhancing the effectiveness of radiation. Some studies have also found that papaverine can slow the growth and spread of non-small cell lung cancer cells.

In this trial, participants will receive papaverine hydrochloride combined with stereotactic body radiation therapy (SBRT). SBRT is already an effective treatment for early-stage non-small cell lung cancer, targeting tumors precisely to destroy cancer cells while minimizing damage to normal tissue. Together, these treatments might prove more effective in treating non-small cell lung cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Jeremy Brownstein, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer or lung metastases from solid tumors, who have not had prior radiation in the same area. They must be physically stable (ECOG 0-2), have a tumor <=5 cm that can be treated with SBRT, and expect to live at least 12 weeks. Participants need proper liver and kidney function, no severe connective tissue disease or pulmonary fibrosis, and agree to use contraception if applicable.

Inclusion Criteria

Histologically or cytologically proven NSCLC for whom SBRT to a single lesion has been chosen as the primary treatment modality (planned dose 50 Gy in 4-5 daily fractions). Patients with lung metastases from solid tumors are eligible.

No prior radiation resulting in overlapping fields

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria

You have had a surgery called pneumonectomy in the past.

You have a history of certain diseases like scleroderma, idiopathic pulmonary fibrosis, or pneumonitis.

Hepatic insufficiency resulting in jaundice and/or coagulation defects, or not meeting laboratory values (albumin, total bilirubin, AST/ALT)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive papaverine hydrochloride IV and undergo SBRT for up to 4-5 sessions over 2 weeks

2 weeks

4-5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

Visits at 4-6 weeks, 3 and 6 months, 1 and 2 years, then every 3 months for 2 years, and every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Papaverine Hydrochloride
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing whether combining papaverine hydrochloride with stereotactic body radiation therapy (SBRT) improves treatment outcomes for non-small cell lung cancer. Papaverine may make cancer cells more sensitive to radiation, while SBRT targets tumors precisely to minimize damage to healthy tissue.

How Is the Trial Designed?

Group I: Treatment (BOLD fMRI, papaverine hydrochloride, SBRT) Experimental Treatment 3 Interventions

Patients undergo BOLD fMRI and receive papaverine hydrochloride IV on days -7 to day 1. Within 30-90 minutes, patients undergo a second BOLD fMRI. Patients then receive papaverine hydrochloride IV and within 30-90 minutes after dose undergo SBRT for a up to 4-5 sessions over 2 weeks. Patients undergo CT scan throughout the study and blood sample collection on study.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Published Research Related to This Trial

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

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]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancers (NSCLCs) that are medically inoperable, providing local control and toxicity levels comparable to surgical resection.

SABR is gaining interest as a noninvasive treatment option for patients with borderline resectable lung cancers, although further randomized studies are needed to evaluate its survival benefits in operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. Iyengar, P., Westover, K., Timmerman, RD.[2013]

Stereotactic ablative radiotherapy (SABR) demonstrated excellent 5-year overall survival (OS) rates of 56.5% and effective local control for patients with isolated recurrent non-small cell lung cancer (NSCLC) after previous treatment, based on a study of 59 patients with a median follow-up of 58.3 months.

The treatment showed minimal toxicity, with only 5% of patients experiencing grade 3 adverse events, indicating that SABR is a safe and effective salvage option for this patient population, comparable to outcomes seen in early-stage NSCLC treated with definitive SABR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non-Small Cell Lung Cancer: A Phase II Clinical Trial. Sun, B., Brooks, ED., Komaki, R., et al.[2022]

In a study of 20 patients with recurrent or metastatic gynecological cancers, CyberKnife stereotactic ablative radiotherapy (SABR) achieved local tumor control in 82% of cases, indicating its efficacy as a treatment option.

The treatment was well-tolerated, with no recorded instances of severe toxicity (grade ≥ 3), suggesting a favorable safety profile for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife Stereotactic Ablative Radiotherapy for Recurrent or Oligometastatic Gynecological Cancers. Kataria, T., Naga, P., Banerjee, S., et al.[2021]

Targeting mitochondrial respiration with the FDA-approved drug papaverine can significantly reduce tumor cells' oxygen demand, leading to improved oxygenation and enhanced effectiveness of radiation therapy.

Papaverine's ability to inhibit mitochondrial complex I is directly linked to increased tumor oxygenation and radiation response, and its derivatives may serve as radiosensitizers with fewer side effects, specifically sparing well-oxygenated normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism. Benej, M., Hong, X., Vibhute, S., et al.[2020]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancer, especially for patients who cannot undergo surgery, showing high local tumor control rates with manageable side effects.

The CyberKnife system is particularly advantageous for SABR in lung tumors due to its ability to accurately target moving tumors during breathing, enhancing treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife stereotactic ablative radiotherapy for lung tumors. Gibbs, IC., Loo, BW.[2022]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Cyberknife stereotactic ablative radiotherapy (SABR) demonstrated a 71.6% objective response rate in 53 patients with unresectable hepatocellular carcinoma (HCC), indicating its efficacy as a salvage treatment when other therapies failed.

The median survival time for patients treated with SABR was 20 months, with 1- and 2-year overall survival rates of 70.1% and 45.4%, respectively, suggesting that while SABR is effective, there is a need to address issues like out-field recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for unresectable hepatocellular carcinoma patients who failed or were unsuitable for transarterial chemoembolization. Lo, CH., Huang, WY., Lee, MS., et al.[2022]

A review of clinical trials from 1970 to 1998 found that most chemical agents used alongside irradiation for cervical cancer did not improve outcomes compared to radiation alone.

However, cisplatin-based therapy combined with concurrent irradiation showed a survival advantage, highlighting its potential effectiveness in treating cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modification of the Radiation Response of Patients With Carcinoma of the Uterine Cervix. Grigsby, PW.[2019]

In a study involving 220 patients with small cell lung cancer (SCLC) who had a response to initial chemotherapy, the PARP inhibitor olaparib did not significantly improve progression-free survival (PFS) compared to placebo, with median PFS of 3.7 months for olaparib versus 2.5 months for placebo.

Common side effects of olaparib included fatigue, nausea, and anemia, and the rate of treatment discontinuation due to toxicity was similar to that seen in other studies, indicating that while olaparib is generally well-tolerated, it does not provide a clear benefit in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib as maintenance treatment in patients with chemosensitive small cell lung cancer (STOMP): A randomised, double-blind, placebo-controlled phase II trial. Woll, P., Gaunt, P., Danson, S., et al.[2022]

In a pilot study of 24 patients with locally advanced cervical cancer, the combination of Carboplatin or Nedaplatin with conventional radiotherapy resulted in a high response rate, with 9 out of 13 evaluable patients achieving complete responses.

The treatment was found to be safe and well-tolerated, with no significant renal damage or severe hematological toxicity, suggesting that these platinum-based drugs could effectively enhance the efficacy of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Concurrent chemoradiotherapy for advanced cervical cancer--a pilot study]. Kodama, J., Hashimoto, I., Seki, N., et al.[2013]

Cisplatin is the primary systemic anti-cancer agent used in conjunction with radiation for locally advanced cervical cancer, but its overall effectiveness is limited.

Recent phase 3 trials show that adding bevacizumab to chemotherapy regimens (cisplatin/paclitaxel or paclitaxel/topotecan) significantly improves overall survival for patients with metastatic or recurrent cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in cervical cancer pharmacotherapies. Markman, M.[2015]

Stereotactic body radiotherapy (SBRT) is effective for treating early-stage non-small cell lung cancer (NSCLC) in patients who cannot undergo surgery, showing good outcomes and low toxicity for tumors located in the periphery.

However, the risk of severe toxicity increases for tumors near critical structures like the bronchial tree or mediastinum, highlighting the importance of careful dose-fractionation planning in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An optimal dose-fractionation for stereotactic body radiotherapy in peripherally, centrally and ultracentrally located early-stage non-small lung cancer. Zarębska, I., Harat, M.[2023]

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Emerging NSCLC treatments: The latest drugs to keep an ... There are multiple radiosensitizers in development, but among the most relevant ones for NSCLC patients is Papaverine Hydrochloride. It will ...

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Papaverine and its derivatives radiosensitize solid tumors ... Our data now show that a single dose of a safe, FDA-approved drug papaverine (PPV) inhibits mitochondrial electron transport chain complex I and ...

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The efficacy of papaverine administration by different ... A recent clinical study has now shown this agent to be capable of decreasing hypoxia in patients with non-small cell lung cancer [128]. Papaverine is an ...

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Papaverine and Stereotactic Body Radiotherapy (SBRT ... This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving papaverine hydrochloride with SBRT may ...

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Study Details | NCT05136846 | Papaverine in Combination ... This phase I trial finds out the best dose, possible benefits and/or side effects of papaverine when given together with chemoradiation intreating patients ...