Papaverine + Radiation Therapy for Rectal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Levodopa

Disqualifiers: Prior pelvic irradiation, Active malignancy, others

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

Compensation: Varies

Number of Visits: 8

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug papaverine (PPV) works when combined with radiation therapy to treat rectal cancer that has spread locally. Researchers aim to determine the optimal dose of PPV and assess the safety and effectiveness of this combination. The trial is open to individuals with locally advanced rectal cancer who wish to avoid surgery after initial treatment. 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 new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, biological therapy, or immunotherapy at least 14 days before starting the study. Additionally, you must not have used levodopa in the last 30 days. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research shows that the safety of using papaverine (PPV) with radiation therapy (RT) to treat rectal cancer is still under investigation. Specific safety data for this combination is not yet available, as it is currently being tested in a phase I clinical trial. This early phase aims to determine safe dosages and identify possible side effects.

As this is an early-stage study, the treatment's safety in humans remains under assessment. Phase I trials typically involve a small number of participants to allow for close monitoring of safety. However, PPV has been used for other medical purposes, suggesting it might be safe when used correctly. It is important to consult a healthcare provider to understand the potential risks and benefits before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about adding papaverine (PPV) to the treatment of rectal cancer because it offers a novel approach compared to the standard care options like mFOLFOX6 or CAPOX. Papaverine is a vasodilator, which means it can enhance blood flow to the tumor area, potentially making radiation therapy more effective. Unlike traditional treatments that primarily target cancer cells directly, papaverine may improve the delivery and impact of radiation by improving oxygenation in the tumor environment. This combination could lead to better outcomes for patients, targeting the cancer more efficiently and possibly reducing the time needed to see significant results.

What evidence suggests that papaverine combined with radiation therapy might be an effective treatment for rectal cancer?

This trial will compare two treatment approaches for rectal cancer. In one arm, participants will receive radiation therapy alone. In the other arm, participants will receive a combination of papaverine and radiation therapy. Research suggests that papaverine, when combined with radiation therapy, might help treat rectal cancer by increasing oxygen levels in tumor cells. More oxygen can make radiation more effective at destroying cancer cells. Studies have shown that papaverine can lower the energy use of tumors, potentially stopping their growth. Surgery often treats rectal cancer but cures only about half of the patients, highlighting the need for additional treatments like this one. Although data from human studies is limited, early results for this combination therapy are promising. ^{1 2 3 4 5}

Who Is on the Research Team?

Terence M Williams

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with rectal cancer that has spread to nearby tissues or lymph nodes but not further. Participants should be able to undergo radiation therapy and surgery if needed, and provide tissue samples. Specific health conditions may exclude some patients.

Inclusion Criteria

My tumor is not highly variable at the genetic level (MSS).

Alanine aminotransferase (ALT) =< 2.5 x ULN (within 30 days of start)

My hemoglobin level is at least 9g/dL, and I haven't had a blood transfusion in the last 14 days.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have taken levodopa in the last 30 days.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo radiation therapy once daily on days 1-5 of week 1

1 week

5 visits (in-person)

Consolidation Chemotherapy

Patients receive standard of care consolidation chemotherapy with either mFOLFOX6 or CAPOX for 3-4 months

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Papaverine
• Radiation Therapy

Trial Overview

The DINOMITE Trial is testing the safety and optimal dosage of papaverine when used with radiation therapy in treating locally advanced rectal cancer. It aims to see if this combination can effectively stop tumor growth by inhibiting certain enzymes.

How Is the Trial Designed?

Group I: Cohort 2 (PPV, RT, CC) Experimental Treatment 9 Interventions

Patients receive PPV IV over 15-30 minutes on day -3 of week 0 and days 1-5 of week 1. Patients also undergo RT QD on days 1-5 (Monday-Friday) of week 1, 1-2 hours after PPV. Starting at week 5, patients receive SOC CC with either mFOLFOX6 or CAPOX for 3-4 months in the absence of disease progression or unacceptable toxicity. As early as four weeks following completion of CC, patients with persistent disease (non-cCR) or disease recurrence in the rectum during disease evaluation may undergo ToME. Additionally, patients undergo two fMRI on study as well as CT, MRI, endoscopy, and blood and tissue sample collection throughout the trial.

Group II: Cohort 1 (RT, CC) Active Control 8 Interventions

Patients undergo RT QD on days 1-5 (Monday-Friday) of week 1. Starting at week 5, patients receive SOC CC with either mFOLFOX6 or CAPOX for 3-4 months in the absence of disease progression or unacceptable toxicity. As early as four weeks following completion of CC, patients with persistent disease (non-cCR) or disease recurrence in the rectum during disease evaluation may undergo ToME. Additionally, patients undergo one fMRI on study as well as CT, MRI, endoscopy, and blood and tissue sample collection throughout the trial.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Capecitabine, when used as part of postoperative chemoradiation for stage II-III rectal cancer, is well tolerated by patients, with a low incidence of severe side effects (grade 3 adverse events) such as diarrhea (12%) and proctitis (7%).

The study involved 41 patients and demonstrated that capecitabine is a convenient treatment option, supporting its use in further research for patients who have undergone radical resection for rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine chemoradiation for rectal cancer after curative surgery. Bajetta, E., Beretta, E., Di Bartolomeo, M., et al.[2015]

The management of locally advanced rectal cancer involves a complex combination of surgery, chemotherapy, and radiation, with treatment tailored based on tumor risk factors identified through MRI and clinical evaluation.

For high-risk patients, preoperative chemoradiation significantly increases the chances of successful surgical resection, while the ongoing PROSPECT trial aims to refine treatment approaches by selectively using chemoradiation based on tumor response, potentially reducing unnecessary treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of neoadjuvant therapy in rectal cancer. Schrag, D.[2022]

The combination of weekly paclitaxel and cisplatin during radiation therapy shows promising efficacy in 'high-risk' cervical cancer patients, with an overall survival rate of 68% at a median follow-up of 58 months.

While hematologic toxicity was common, it was manageable and did not frequently cause treatment delays; however, significant late complications occurred in 52% of patients, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. Argenta, PA., Ghebre, R., Dusenbery, KE., et al.[2020]

Concurrent radiotherapy with chemotherapy (5-fluorouracil and mitomycin-C) is an established treatment for anal canal squamous cell carcinoma, but there is potential for improving tumor control and reducing side effects.

Recent studies are exploring newer chemotherapeutic agents like cisplatin and capecitabine, as well as advanced radiation techniques like intensity-modulated radiation therapy, to enhance treatment efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging treatment strategies for anal cancer. Meyer, J., Willett, C., Czito, B.[2021]

Surgery remains the most effective treatment for rectal cancer, but it only cures about 50% of patients, highlighting the need for additional therapies.

Combining radiation therapy with chemotherapy after surgery has shown a synergistic effect that improves survival rates, suggesting that this approach may be a key strategy in future rectal cancer treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival. Sexe, R., Miedema, BW.[2005]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06834126

Study Details | NCT06834126 | Papaverine in Combination ...

This phase I trial studies the side effects and best dose of papaverine (PPV) when given together with radiation therapy (RT) and tests how well it works in ...

2.

targetedonc.com

targetedonc.com/view/dinomite-trial-explores-papaverine-plus-radiation-in-rectal-cancer

DINOMITE Trial Explores Papaverine Plus Radiation in ...

The phase 1 trial will test the combination of papaverine and radiation therapy when given to patients with rectal cancer that has spread to nearby tissue or ...

3.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/577818

Papaverine in Combination With Radiation Therapy for the ...

Giving PPV with RT may be safe, tolerable, and/or effective in treating patients with locally advanced rectal cancer. Show more ...

4.

journals.lww.com

journals.lww.com/oncology-times/fulltext/2025/09000/dinomite_tests_papaverine_in_rectal_cancer_therapy.7.aspx

DINOMITE Tests Papaverine in Rectal Cancer Therapy

“Denko and his team, as well as my research team, established that papaverine effectively reduces tumor consumption, thereby raising levels of oxygen within ...

5.

withpower.com

withpower.com/trial/phase-1-rectal-neoplasms-5-2025-d4a08

Papaverine + Radiation Therapy for Rectal Cancer

Surgery remains the most effective treatment for rectal cancer, but it only cures about 50% of patients, highlighting the need for additional therapies.