Ignite Creation Date:
2025-12-24 @ 1:04 PM
Ignite Modification Date:
2026-01-11 @ 9:23 AM
Study NCT ID:
NCT05385861
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2025-08-15
First Post:
2022-05-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Nal-IRI (ONIVYDE® ) and Carboplatin in Patients With Advanced or Metastatic GEP-NET
Sponsor:
National Health Research Institutes, Taiwan
Organization:
Study Overview
Official Title:
A Phase I/II Study of Nal-IRI (ONIVYDE® ) and Carboplatin in Patients With Advanced or Metastatic Gastroenteropancreatic Poorly Differentiated Neuroendocrine Carcinoma
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The current study is an investigator-initiated, single-arm phase 1/2 study that enrolled patients with advanced or recurrent and/or metastatic gastroenteropancreatic poorly differentiated neuroendocrine carcinoma for the treatment of nal-IRI (ONIVYDE®) plus carboplatin as the first-line chemotherapy.
Detailed Description:
Eligible patients will be treated into two cohorts.
In adaptive phase 1 cohort:
Six patients will be enrolled in safety run-in cohort of dose level 0. If less than 2 patients experience dose-limiting toxicity (DLT) in dose level 0, dose level 1 will be tested. However, if more than 1 patients experience DLT in dose level 0, dose level -1 will be tested. The MTD at which no more than 1 of the 6 patients experience DLT will be determined for the phase 2 cohort. Otherwise, additional 6 patients will be tested in the dose level -1. Based on results from safety run-in cohort, PR2D will be determined. The evaluable patients in RP2D cohort will be incorporated into phase 2 cohort for final analysis.
Dose in phase 1 cohort:
Dose level 1= onivyde 100 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Dose level 0= onivyde 80 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Dose level -1= onivyde 60 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Carboplatin dose (mg) is calculated by the Calvert formula: AUC x (eGFR + 25). Cockcroft-Gault equation: eGFR (calculated Ccr)= \[(140-age) x weight x 0.85 (if female)\] / (72 x serum Cr). The maximum eGFR for dose calculation is 125 ml/min.
The definition of DLT:
Following toxicities occur during the first cycle of the combination chemotherapy with nal-IRI (ONIVYDE®) and carboplatin will be considered as DLTs. Toxicities are assessed by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
* Grade 4 neutropenia (ANC \< 500/μL) ≥3 days' duration under primary G-CSF support
* Grade 3 or higher neutropenia (ANC \< 1,000/μL) with concurrent active infection requiring IV antibiotics treatment
* Grade 4 thrombocytopenia (platelet counts \< 25,000/μL)
* Grade 3 thrombocytopenia (platelet counts \< 50,000/μL) associated with active bleeding that transfusion is required
* Any grade 3 or higher treatment-related non-hematologic toxicity (except for anorexia/nausea, vomiting, and asthenia/fatigue)
* Any adverse drug reactions lead to more than 3 weeks delay
In Phase 2 Cohort Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the treatment discontinuation criteria.
Tumor response will be assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) every 6 weeks.
Adverse events (AEs) will be evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Patients sign additional consent to participate in the next generation sequencing study will be required to have extra tissue samplings at the study entry.
A follow-up visit is required approximately 30 days after treatment discontinuation. Overall survival status will be followed by clinic visit or by phone every 3 months until death or the maximum of 3 years, whichever occurs first.
In adaptive phase 1 cohort:
Six patients will be enrolled in safety run-in cohort of dose level 0. If less than 2 patients experience dose-limiting toxicity (DLT) in dose level 0, dose level 1 will be tested. However, if more than 1 patients experience DLT in dose level 0, dose level -1 will be tested. The MTD at which no more than 1 of the 6 patients experience DLT will be determined for the phase 2 cohort. Otherwise, additional 6 patients will be tested in the dose level -1. Based on results from safety run-in cohort, PR2D will be determined. The evaluable patients in RP2D cohort will be incorporated into phase 2 cohort for final analysis.
Dose in phase 1 cohort:
Dose level 1= onivyde 100 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Dose level 0= onivyde 80 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Dose level -1= onivyde 60 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk Carboplatin dose (mg) is calculated by the Calvert formula: AUC x (eGFR + 25). Cockcroft-Gault equation: eGFR (calculated Ccr)= \[(140-age) x weight x 0.85 (if female)\] / (72 x serum Cr). The maximum eGFR for dose calculation is 125 ml/min.
The definition of DLT:
Following toxicities occur during the first cycle of the combination chemotherapy with nal-IRI (ONIVYDE®) and carboplatin will be considered as DLTs. Toxicities are assessed by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
* Grade 4 neutropenia (ANC \< 500/μL) ≥3 days' duration under primary G-CSF support
* Grade 3 or higher neutropenia (ANC \< 1,000/μL) with concurrent active infection requiring IV antibiotics treatment
* Grade 4 thrombocytopenia (platelet counts \< 25,000/μL)
* Grade 3 thrombocytopenia (platelet counts \< 50,000/μL) associated with active bleeding that transfusion is required
* Any grade 3 or higher treatment-related non-hematologic toxicity (except for anorexia/nausea, vomiting, and asthenia/fatigue)
* Any adverse drug reactions lead to more than 3 weeks delay
In Phase 2 Cohort Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the treatment discontinuation criteria.
Tumor response will be assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) every 6 weeks.
Adverse events (AEs) will be evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Patients sign additional consent to participate in the next generation sequencing study will be required to have extra tissue samplings at the study entry.
A follow-up visit is required approximately 30 days after treatment discontinuation. Overall survival status will be followed by clinic visit or by phone every 3 months until death or the maximum of 3 years, whichever occurs first.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: