Papaverine combined with radiation therapy for advanced rectal cancer
DINOMITE (Decreasing Hypoxia With Mitochondrial Inhibition in Locally Advanced Rectal Cancer): Phase 1 Trial of Papaverine in Combination With Radiation
This study is testing if adding papaverine to radiation therapy can help people with advanced rectal cancer feel better and improve their treatment results.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | Chemotherapy, immunotherapy, radiation |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT06834126 on ClinicalTrials.gov |
What this trial studies
This phase I trial investigates the safety and optimal dosage of papaverine (PPV) when used alongside radiation therapy (RT) in patients with locally advanced rectal cancer. The study aims to determine the maximum tolerated dose of PPV and assess its effectiveness in improving treatment outcomes. It also explores various secondary objectives, including the clinical response rates and survival metrics, as well as the potential impact of PPV on tumor hypoxia and the immune microenvironment. Participants will undergo various assessments, including imaging and biospecimen collection, to evaluate the treatment's efficacy.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed locally advanced rectal adenocarcinoma who are seeking non-operative management after total neoadjuvant therapy.
Not a fit: Patients with microsatellite instability-high tumors or those who do not wish to pursue an organ preservation approach may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could enhance treatment effectiveness and improve survival rates for patients with locally advanced rectal cancer.
How similar studies have performed: While this approach is novel, similar studies combining targeted therapies with radiation have shown promise in other cancer types.
Eligibility criteria
Show full inclusion / exclusion criteria
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)
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Terence M Williams — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.