Trials / Active Not Recruiting
Active Not RecruitingNCT04234568
Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors
A Phase I Trial of Triapine and Lutetium Lu 177 Dotatate in Combination for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
- Status
- Active Not Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 31 (actual)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase I trial studies the side effects and best dose of triapine when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. Giving triapine and lutetium Lu 177 dotatate together may work better to treat patients with neuroendocrine tumors.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the safety and to determine the recommended phase 2 dose (RP2D) of lutetium Lu 177 dotatate in combination with triapine. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 2, 4, 6, and 8 months post therapy in dose escalation cohort. III. To determine the best overall response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in dose expansion cohort. IV. To measure duration of response (DOR) associated with the combination. V. To evaluate progression-free survival (PFS), 24-month PFS, and overall survival (OS). CORRELATIVE OBJECTIVES: I. Measure baseline 68 gallium-dotatate (or copper 64 dotatate) biodistribution. II. Evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin level by venous blood gas proportion. III. Collect blood at baseline and at disease progression to correlate result with clinical outcome. (NOTE: originally this blood was collected to analyze hPG80 but will now the frozen blood samples will be biobanked for future correlative analysis) IV. Describe the tumor molecular profile using whole exome sequencing (WES), as well as ribonucleic acid sequencing (RNAseq) by the National Clinical Laboratory Network (NCLN), and correlate it with treatment outcome. V. Collect plasma for circulating deoxyribonucleic acid (DNA) (ctDNA) assessment. VI. Assess the effect of triapine on single deoxyribonucleoside concentrations by a liquid chromatography-mass spectrometry (LC/MSMS) assay in baseline (pre-treatment) and disease progression blood samples (processed to plasma). OUTLINE: This is a dose-escalation study of triapine followed by a dose-expansion study. Patients receive lutetium Lu 177 dotatate intravenously (IV) for 30 to 40 minutes on day 1 of each cycle and triapine orally (PO) on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) scan throughout the trial. Patients undergo blood specimen collection on study. Patients are followed up every 3 months for 24 months from the time of enrollment. Patients removed from study for unacceptable adverse event(s) are followed until resolution or stabilization of the adverse event.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biospecimen Collection | Correlative studies |
| PROCEDURE | Computed Tomography | Undergo CT |
| DRUG | Lutetium Lu 177 Dotatate | Given IV |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| DRUG | Triapine | Given PO |
Timeline
- Start date
- 2020-07-20
- Primary completion
- 2024-09-17
- Completion
- 2026-03-14
- First posted
- 2020-01-21
- Last updated
- 2025-12-22
- Results posted
- 2025-11-03
Locations
11 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04234568. Inclusion in this directory is not an endorsement.