Papaverine + Chemoradiation for Lung Cancer

Recruiting at 1 trial location

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ohio State University Comprehensive Cancer Center

Must be taking: Chemotherapy

Disqualifiers: Pneumonectomy, Scleroderma, Pulmonary fibrosis, others

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

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well papaverine works with standard chemoradiation to treat non-small cell lung cancer (NSCLC) at stages II and III. Papaverine, a drug targeting the energy supply of cancer cells, aims to slow their growth. The trial seeks to determine the optimal dose and assess whether this combination improves treatment outcomes and reduces side effects. It suits those with NSCLC that cannot be surgically removed and who have been recommended for chemoradiation by a medical team. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get specific guidance based on your situation.

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

Research has shown that papaverine, an FDA-approved drug, has been safely used for other conditions. It affects how cells produce energy, which might help slow cancer growth. Some studies suggest it is generally well-tolerated. However, like any drug, it can have side effects, so careful monitoring during treatment remains important.

Paclitaxel and carboplatin are already approved for treating non-small cell lung cancer and other cancers. Their long-term use has provided extensive safety information. Paclitaxel can cause side effects like lowering white blood cell counts, increasing the risk of infection. Carboplatin also has side effects but is generally considered safe for lung cancer treatment.

This trial combines papaverine with these established treatments. The goal is to find the best dose and identify any new side effects. As an early phase study, it focuses on understanding the safety and how well patients can tolerate these combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for lung cancer, like chemotherapy with carboplatin and paclitaxel, work by attacking rapidly dividing cancer cells. But this new treatment adds papaverine, a drug known for its ability to increase blood flow, potentially enhancing the effectiveness of radiation therapy. Researchers are excited because papaverine might make cancer cells more sensitive to radiation, potentially improving treatment outcomes. This approach aims to offer a more effective attack on the cancer by combining the existing chemotherapy and radiation with a novel strategy to weaken the cancer cells' defenses.

What evidence suggests that papaverine combined with chemoradiation might be an effective treatment for non-small cell lung cancer?

Research has shown that papaverine, which participants in this trial may receive, might enhance radiation treatment by increasing oxygen levels in tumors, making them more responsive. It also slows the growth and spread of non-small cell lung cancer cells. Paclitaxel, another drug in this trial, has shrunk tumors in about 30% of patients with advanced non-small cell lung cancer. Carboplatin, also part of the treatment regimen, is often combined with other treatments for this cancer type and has been linked to better survival rates in some studies. Together, these treatments aim to combat cancer from different angles, potentially leading to better patient outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Jeremey Brownstein, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with stage II-III non-small cell lung cancer that hasn't spread beyond the original site and is considered inoperable. Participants must have a life expectancy over 6 months, be well enough for chemotherapy with radiation, and not have had certain other cancers or treatments within specific time frames. They should also not be pregnant or breastfeeding and agree to use contraception.

Inclusion Criteria

Your hemoglobin level has to be at least 9 grams per deciliter within 30 days before joining the study.

My lung cancer is confirmed to be non-small cell type.

My lung cancer is at stage II-III, according to the AJCC.

Exclusion Criteria

I have liver problems causing yellowing of my skin or eyes and issues with blood clotting.

I haven't had chemotherapy or targeted therapy for over 2 years.

I have a history of scleroderma or idiopathic pulmonary fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive papaverine in combination with chemoradiation for 6 weeks

6 weeks

5 visits per week (in-person)

Immunotherapy

Patients with PD-L1 positive disease receive durvalumab every 2 weeks for 12 months

12 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 1, 3, 6, 9, 12, 16, 20, and 24 months, then periodically up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Papaverine
• Radiation Therapy

Trial Overview The trial is testing the effectiveness of papaverine combined with chemoradiation therapy (using carboplatin and paclitaxel) on patients with non-small cell lung cancer. Papaverine aims to slow down cancer growth by targeting mitochondrial metabolism.

How Is the Trial Designed?

Group I: Treatment (papaverine, RT, paclitaxel, carboplatin) Experimental Treatment 12 Interventions

Patients receive PPV IV or SC over 30 minutes and patients receiving chemoradiation undergo 5 fractions of RT per week for 6 weeks or 5 fractions of hypofractionated RT per week for 3 weeks without chemotherapy. Patients undergoing chemoradiation receive paclitaxel IV and carboplatin IV QW over 1-6 weeks or pemetrexed IV followed by carboplatin IV every 3 weeks during radiation in the absence of disease progression or unacceptable toxicity. Patients with PD-L1 positive disease may also receive durvalumab after completing CRT as considered clinically appropriate by the treating medical oncologist. Patients also undergo PET/CT or CT and brain MRI during screening, and blood sample collection, MRI and CT scans throughout the trial.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II study involving 43 patients with locally advanced unresectable non-small cell lung cancer, the combination of weekly paclitaxel and carboplatin with hyperfractionated radiation therapy resulted in a high overall response rate of 78.6%, with 7.2% achieving a complete response.

The treatment was generally well-tolerated, although esophagitis was a significant side effect, affecting 26% of patients with grade 3 or 4 toxicity, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study). Choy, H., Devore, RF., Hande, KR., et al.[2019]

In a study of 41 women with early-stage uterine papillary serous carcinoma (UPSC), the combination of concurrent adjuvant intravaginal radiation therapy (IVRT) and carboplatin/paclitaxel chemotherapy resulted in impressive 5-year disease-free survival (DFS) and overall survival (OS) rates of 85% and 90%, respectively, after a median follow-up of 58 months.

The treatment was well-tolerated, with 85% of patients completing all planned cycles, and there were no vaginal recurrences, indicating the regimen's efficacy and safety for early-stage UPSC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year outcomes of adjuvant carboplatin/paclitaxel chemotherapy and intravaginal radiation for stage I-II papillary serous endometrial cancer. Kiess, AP., Damast, S., Makker, V., et al.[2019]

A systematic review of 31 studies involving 3090 patients treated with cisplatin-etoposide and 48 studies with 3728 patients treated with carboplatin-paclitaxel showed that both chemotherapy regimens had similar efficacy in treating unresectable stage III non-small-cell lung cancer, with no significant differences in overall survival or progression-free survival.

However, carboplatin-paclitaxel was associated with fewer severe hematological toxic effects compared to cisplatin-etoposide, making it a safer option for patients undergoing concurrent thoracic radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non-Small-Cell Lung Cancer: A Systematic Review. Steuer, CE., Behera, M., Ernani, V., et al.[2022]

The study established that the maximum tolerated dose (MTD) for carboplatin in combination with weekly paclitaxel is AUC 2.5, indicating a safe dosage for further testing in phase II trials.

Weekly chemoradiotherapy with paclitaxel and carboplatin is feasible and shows promising efficacy, with a 2-year progression-free survival (PFS) rate of 80% and overall survival (OS) rate of 86% in patients with locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of weekly paclitaxel, weekly carboplatin, and concurrent radiotherapy for primary cervical cancer. Rao, GG., Rogers, P., Drake, RD., et al.[2015]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

The maximum-tolerated dose (MTD) of paclitaxel when combined with cisplatin and pelvic radiotherapy for cervical cancer patients was determined to be 50 mg/m2 per week, with diarrhea identified as the main dose-limiting toxicity.

In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating that this regimen could be an effective option for treating locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. Pignata, S., Frezza, P., Tramontana, S., et al.[2020]

Cisplatin combined with other agents like vinblastine or etoposide shows promise as an effective pre-radiotherapy treatment for locally advanced non-small cell lung cancer (NSCLC), but optimal scheduling is still being researched.

In a study of 170 patients, concurrent chemotherapy with carboplatin and radiation led to increased toxicity, including significantly higher rates of neutropenia and thrombocytopenia, indicating that while this approach may improve treatment efficacy, it also raises safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. Bishop, JF.[2019]

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]

In a phase III trial involving 200 patients with stage III non-small cell lung cancer, the chemotherapy regimen of etoposide and cisplatin (EP) showed a significantly higher 3-year overall survival rate compared to carboplatin and paclitaxel (PC), with a difference of 15% (P = 0.024).

While EP demonstrated better overall survival, it was associated with a higher incidence of severe esophagitis (20% vs. 6.3% for PC), whereas PC had a higher rate of radiation pneumonitis (33.3% vs. 18.9% for EP), indicating a trade-off in safety profiles between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Liang, J., Bi, N., Wu, S., et al.[2020]

In a study of 271 patients with high-risk cervical cancer, sequential treatment with paclitaxel and carboplatin followed by radiation showed a 5-year survival rate of 85.8%, compared to 78.9% for simultaneous cisplatin-based radiochemotherapy, although the difference was not statistically significant (P = 0.25).

The sequential treatment resulted in lower rates of severe hematological toxicity and early treatment termination compared to the simultaneous approach, suggesting it may be a safer alternative when immediate postoperative radiation is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Sehouli, J., Runnebaum, IB., Fotopoulou, C., et al.[2023]

In a Phase I/II trial involving 17 patients with Stage III nonsmall cell lung cancer (NSCLC), the combination of paclitaxel and radiation therapy (60 Gy over 6 weeks) was found to be safe, with a recommended dose of 120 mg/m2 leading to a high response rate of 78%.

The main side effect observed was neutropenia, particularly at the highest dose, but there were no serious infections related to the treatment, indicating that while the combination is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of paclitaxel (TAXOL) and concurrent radiotherapy in advanced nonsmall cell lung cancer. Kirkbride, P., Gelmon, K., Eisenhauer, E., et al.[2019]

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