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Papaverine in Combination With Radiation Therapy for the Treatment of Locally Advanced Rectal Cancer, DINOMITE Trial

ConditionsLocally Advanced Rectal AdenocarcinomaStage II Rectal Cancer AJCC v8Stage III Rectal Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About 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 does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood and tissue sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Consolidation Therapy

    Drug

    Receive CC with mFOLFOX6 or CAPOX

  • Functional Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo fMRI

  • Gastrointestinal Endoscopy

    Procedure/Surgery

    Undergo endoscopy

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Papaverine

    Drug

    Given IV

  • Radiation Therapy

    Radiation

    Undergo RT

  • Total Mesorectal Excision

    Procedure/Surgery

    Undergo ToME

Treatment groups

36 Participants
are divided into 2 treatment groups
Group A: Cohort 1 (RT, CC)Active comparator 8 interventions
Group B: Cohort 2 (PPV, RT, CC)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

Acute dose limiting toxicity (DLT)

As assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. A defined adverse event considered to be possibly, probably, or definitely related to study treatment (radiation therapy or PPV). Will employ the time-to-event Bayesian optimal interval design (TITE-BOIN) to find the maximum tolerated dose (MTD).

Time frame
From time of single-agent papaverine (PPV) week 0 treatment to start of consolidation chemotherapy (CC), assessed up to 4 weeks
2

Late DLT

As assessed by NCI CTCAE v5.0. A defined adverse event considered to be possibly, probably, or definitely related to study treatment (radiation therapy or PPV). Will employ the TITE-BOIN design to find the MTD.

Time frame
From the start of CC week 5 treatment to 12 months from week 0
3

Incidence of treatment related adverse events during acute DLT period

As assessed by NCI CTCAE v5.0. Will be delineated by grade and attribution. A defined adverse event considered to be possibly, probably, or definitely related to study treatment (radiation therapy or PPV).

Time frame
From time of single-agent PPV week 0 treatment to start of CC, assessed up to 4 weeks
4

Incidence of treatment related adverse events during late DLT period

As assessed by NCI CTCAE v5.0. Will be delineated by grade and attribution. A defined adverse event considered to be possibly, probably, or definitely related to study treatment (radiation therapy or PPV).

Time frame
From the start of CC week 5 treatment to 12 months from week 0

Secondary outcomes

1

Clinical complete response rate

Will be defined as percent of evaluable patients having no evidence of disease as assessed by magnetic resonance imaging/endoscopy. Will be summarized by cohort and dose level.

Time frame
From time of single agent papaverine (PPV) week 0 treatment to completion of consolidation chemotherapy (CC), assessed up to 20 weeks.
2

Local-regional control rate

Will be defined as percent of evaluable patients having no evidence of pelvic recurrence in the areas of the primary tumor and regional lymph nodes.

Time frame
From time of single agent papaverine (PPV) week 0 treatment to completion of consolidation chemotherapy (CC), assessed up to 20 weeks.
3

Local-regional recurrence free survival

Time frame
From enrollment to date of first local regional recurrence, death as a result of any cause or being censored at last contact, assessed up to 5 years
4

Total mesorectal excision free survival

Time frame
From enrollment to date of total mesorectal surgical excision, death as result of any cause or being censored at last contact, assessed up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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