Papaverine + Radiation Therapy for Rectal Cancer

Recruiting in Palo Alto (17 mi)

Overseen ByTerence M Williams

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: City of Hope Medical Center

No Placebo Group

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.

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).

I am 18 years old or older.

My kidney function, measured by creatinine clearance, is adequate.

My diagnosis is rectal cancer confirmed by tissue analysis.

My rectal cancer is advanced but hasn't spread to distant organs.

I can do most of my daily activities on my own.

I have HIV, HCV, or HBV with an undetectable viral load.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have had radiation therapy in the pelvic area that overlapped.

I have had a complete heart block, liver issues like cirrhosis, or prolonged erections.

Participant Groups

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.

2Treatment groups

Experimental Treatment

Active Control

Group I: Cohort 2 (PPV, RT, CC)Experimental Treatment9 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 Control8 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.