Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors
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|ClinicalTrials.gov Identifier: NCT04234568|
Recruitment Status : Not yet recruiting
First Posted : January 21, 2020
Last Update Posted : February 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Digestive System Neuroendocrine Tumor Metastatic Well Differentiated Neuroendocrine Neoplasm||Drug: Lutetium Lu 177 Dotatate Drug: Triapine||Phase 1|
I. To evaluate the safety and to determine the recommended phase 2 dose (RP2D) of lutetium Lu 177 dotatate in combination with triapine.
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.
III. To measure duration of response (DOR) associated with the combination. IV. To evaluate progression-free survival (PFS), 24-month PFS, and overall survival (OS).
I. Measure baseline 68 gallium-dotatate biodistribution. II. Evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin level by venous blood gas proportion.
III. Evaluate NETest at baseline and disease progression to correlate result with clinical outcome.
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) Genomics Lab, and correlate it with treatment outcome.
V. Collect plasma for circulating deoxyribonucleic acid (DNA) (ctDNA) assessment.
OUTLINE: This is a dose-escalation study of triapine.
Patients receive lutetium Lu 177 dotatate intravenously (IV) over 30-40 minutes on day 1 and triapine orally (PO) once daily (QD) on days 1-4. Treatment repeats every 8 weeks (56 days) for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 24 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Triapine and Lutetium Lu 177 Dotatate in Combination for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)|
|Estimated Study Start Date :||November 6, 2020|
|Estimated Primary Completion Date :||January 15, 2022|
|Estimated Study Completion Date :||January 15, 2022|
Experimental: Treatment (lutetium Lu 177 dotatate, triapine)
Patients receive lutetium Lu 177 dotatate IV over 30-40 minutes on day 1 and triapine PO QD on days 1-4. Treatment repeats every 8 weeks (56 days) for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Lutetium Lu 177 Dotatate
- Maximum tolerated dose (MTD) of triapine [ Time Frame: 8 weeks (56 days) ]The MTD will be estimated using isotonic regression based on observed dose limiting toxicity from all patients enrolled in the phase 1 portion and expansion cohort. All patients who received study drugs will be included in the safety analysis.
- Dose limiting toxicity (DLT) [ Time Frame: 8 weeks (56 days) ]DLTs will be summarized descriptively at each dose level. Will be summarized based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade of toxicity for each adverse event category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. Will describe all serious (>= grade 3) toxicity events on a patient-by-patient basis. Frequency and incidence tables of toxicity and adverse events will be generated in the overall patient group and by dose level depending on patient enrollment.
- Overall response rate (ORR) [ Time Frame: 24 months ]ORR will be estimated along with 95% exact binomial confidence interval.
- Progression free survival (PFS) [ Time Frame: 24 months ]Will be estimated using the Kaplan-Meier curve and median estimates and confidence intervals will be calculated.
- Overall survival [ Time Frame: 24 months ]Will be estimated using the Kaplan-Meier curve and median estimates and confidence intervals will be calculated.
- NETest [ Time Frame: Up to 24 months ]Will be summarized using descriptive statistics and changes from baseline versus follow-up time points will be assessed using paired test methodologies.
- Expression of somatostatin receptors [ Time Frame: Up to 24 months ]Will be summarized using descriptive statistics and changes from baseline versus follow-up time points will be assessed using paired test methodologies.
- Whole exome sequencing [ Time Frame: 24 months ]Will be processed using the data processing and data analysis pipelines from the Biostatistics and Bioinformatics shared resource of Markey Cancer Center (MCC) to identify candidate mutated genes with adjustment for false discovery rate.
- Pharmacokinetic (PK) studies [ Time Frame: 24 months ]PK parameters will be estimated from patients enrolled in the dose escalation portion of the phase 1 trial. PK parameters will be compared with historical controls, and exploratorily, we may correlate exposure to toxicity, and incorporate data into a population PK model.
- Krenning score from the gallium 68 dotatate [ Time Frame: 24 months ]Will be summarized by calculating the proportion of patients in each Krenning score category and exploratory assessments for association with clinical response (ORR) will be performed using Fisher's exact test. Median, interquartile range will be calculated for quantitative image measurements from gallium 68 dotatate and exploratory comparison of levels with clinical response (ORR) will be performed using two sample t-test or nonparametric analogs. Correlative endpoint analyses will be based on patients who received the recommended phase 2 dose from the dose escalation portion and expansion cohort.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04234568
|Principal Investigator:||Aman Chauhan||Ohio State University Comprehensive Cancer Center LAO|