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

Trial Summary

What is the purpose of this trial?

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 treating patients with rectal cancer that has spread to nearby tissue or lymph nodes (locally advanced). PPV is an enzyme inhibitor, and it may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. RT uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Giving PPV with RT may be safe, tolerable, and/or effective in treating patients with locally advanced rectal cancer.

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.

What data supports the effectiveness of the treatment Papaverine + Radiation Therapy for Rectal Cancer?

While there is no direct data on Papaverine combined with radiation for rectal cancer, radiation therapy is known to help prevent local recurrence and potentially increase survival in rectal cancer patients. Combining radiation with chemotherapy has shown a synergistic effect, improving outcomes, which suggests that combining radiation with other agents like Papaverine might also be beneficial. ^{1 2 3 4 5}

Is the combination of Papaverine and Radiation Therapy safe for humans?

There is no specific safety data available for the combination of Papaverine and Radiation Therapy. However, radiation therapy alone can cause side effects like diarrhea and rectal inflammation, and other treatments like amifostine have been studied to reduce these effects. ^{6 7 8 9 10}

How does the Papaverine + Radiation Therapy treatment for rectal cancer differ from other treatments?

Papaverine + Radiation Therapy for rectal cancer is unique because it combines a vasodilator (a drug that widens blood vessels) with radiation therapy, potentially enhancing the delivery and effectiveness of radiation by improving blood flow to the tumor. This approach differs from standard treatments that typically use chemotherapy drugs like 5-fluorouracil or capecitabine with radiation. ^{1 8 11 12 13}

Research Team

Terence M Williams

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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2. United States pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival. [2005]

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6. Switzerland pubmed.ncbi.nlm.nih.gov

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9. England pubmed.ncbi.nlm.nih.gov

Capecitabine chemoradiation for rectal cancer after curative surgery. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Prevention of acute radiation-induced rectal toxicity by amifostine: efficacy and evaluation of objective and subjective endpoints for radiation therapy-induced mucositis. [2020]

11. Singapore pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

The potential role of amifostine in conjunction with cisplatin in the treatment of locally advanced carcinoma of the cervix. [2013]

13. United States pubmed.ncbi.nlm.nih.gov

Current and emerging treatment strategies for anal cancer. [2021]