Recruiting
Phase 1

Papaverine & Radiation

Sponsor:

City of Hope Medical Center

Code:

NCT06834126

Conditions

Locally Advanced Rectal Adenocarcinoma

Stage II Rectal Cancer AJCC v8

Stage III Rectal Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Consolidation Therapy

Functional Magnetic Resonance Imaging

Gastrointestinal Endoscopy

Study Details

Brief summary:

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.

Conditions

Locally Advanced Rectal Adenocarcinoma

Stage II Rectal Cancer AJCC v8

Stage III Rectal Cancer AJCC v8

Study ID

NCT06834126

Start date

Apr 7, 2025

Status verified date

Jul, 2026

Completion date

Sep 19, 2028

Anticipated

Primary completion date

Sep 19, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative
  • Willingness to participate in all correlative studies: fMRI, and tissue collection of tumor and normal rectum (ribonucleic acid \[RNA\]/deoxyribonucleic acid \[DNA\]/protein), blood (plasma/peripheral blood mononuclear cell \[PBMC\]) draws and stool collection
  • Age: ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Histologically confirmed rectal adenocarcinoma
  • Patient wants to pursue an organ preservation/non-operative management (NOM) approach after completion of total neoadjuvant therapy (TNT)
  • Locally advanced rectal cancer (T3-4 or node+, M0)
  • Tumor is microsatellite stable (MSS) (defined as not microsatellite instability-high \[MSI-H\] or mismatch repair deficient \[dMMR\])
  • Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (within 30 days of start). NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • Platelets ≥ 100,000/mm\^3 (within 30 days of start). NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
  • Hemoglobin ≥ 9g/dL (within 30 days of start). NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
  • Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (within 30 days of start)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (within 30 days of start)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (within 30 days of start)
  • Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 30 days of start)
  • For patients with known infections only: seropositive for HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial (within 28 days of start)
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (within 30 days of start)
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of protocol therapy

  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

  • Chemotherapy, biological therapy, immunotherapy within 14 days or five half-lives (whichever is shorter) prior to day 1 of protocol therapy
  • Prior pelvic irradiation resulting in overlapping fields
  • Use of levodopa in the last 30 days
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • Unable to undergo MRI and endoscopic procedures
  • History of complete atrioventricular block, hepatic dysfunction (e.g. cirrhosis), or priapism
  • Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Design

Enrollment

36 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Cohort 1 (RT, CC)

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.

experimental: Cohort 2 (PPV, RT, CC)

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.

Interventions

Biospecimen Collection

Undergo blood and tissue sample collection

Computed Tomography

Undergo CT

Consolidation Therapy

Receive CC with mFOLFOX6 or CAPOX

Functional Magnetic Resonance Imaging

Undergo fMRI

Gastrointestinal Endoscopy

Undergo endoscopy

Magnetic Resonance Imaging

Undergo MRI

Papaverine

Given IV

Radiation Therapy

Undergo RT

Total Mesorectal Excision

Undergo ToME

Primary outcome measure

  • Acute dose limiting toxicity (DLT) [ Time Frame: From time of single-agent papaverine (PPV) week 0 treatment to start of consolidation chemotherapy (CC), assessed up to 4 weeks ]
  • Late DLT [ Time Frame: From the start of CC week 5 treatment to 12 months from week 0 ]
  • Incidence of treatment related adverse events during acute DLT period [ Time Frame: From time of single-agent PPV week 0 treatment to start of CC, assessed up to 4 weeks ]
  • Incidence of treatment related adverse events during late DLT period [ Time Frame: From the start of CC week 5 treatment to 12 months from week 0 ]

Central Contacts and Locations

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Terence M. Williams

626-218-2332terwilliams@coh.org

Principal Investigator:

Terence M. Williams

More Information

Sponsor

City of Hope Medical Center

Last update posted

Jul 22, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-07-22.