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Nal-IRI (ONIVYDE® ) and Carboplatin in Patients With Advanced or Metastatic GEP-NET

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05385861
Recruitment Status : Not yet recruiting
First Posted : May 23, 2022
Last Update Posted : May 23, 2022
Sponsor:
Collaborators:
Taipei Veterans General Hospital, Taiwan
Chang Gung Memorial Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Information provided by (Responsible Party):
National Health Research Institutes, Taiwan

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.

Condition or disease Intervention/treatment Phase
GEP-NET Drug: nanoliposomal irinotecan plus carboplatin Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: an investigator-initiated, single-arm phase 1/2 study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Nal-IRI (ONIVYDE® ) and Carboplatin in Patients With Advanced or Metastatic Gastroenteropancreatic Poorly Differentiated Neuroendocrine Carcinoma
Estimated Study Start Date : July 1, 2022
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024


Arm Intervention/treatment
Experimental: nal-IRI (ONIVYDE®) and Carboplatin
nal-IRI (ONIVYDE®) and Carboplatin
Drug: nanoliposomal irinotecan plus carboplatin

Dose in phase 1 cohort:

Dose level 1= nanoliposomal irinotecan 100 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk

Dose level 0= nanoliposomal irinotecan 80 mg/m2 plus carboplatin AUC=4, intravenously both on day 1, q3wk

Dose level -1= nanoliposomal irinotecan 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.

In Phase 2 Cohort Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the treatment discontinuation criteria.

Other Names:
  • Phase 1 cohort
  • Phase 2 Cohort




Primary Outcome Measures :
  1. MTD and RP2D [ Time Frame: 3 Years ]
    • in phase 1 cohort, to determine MTD (maximum tolerated dose) and recommended phase 2 dose (RP2D)

  2. tumor response rate [ Time Frame: 3 Years ]
    • in phase 2 cohort, to assess the objective tumor response rate


Secondary Outcome Measures :
  1. PFS and OS [ Time Frame: 3 Years ]
    • to assess other efficacy variables, including disease control rate, progression free survival (PFS), and overall survival (OS)

  2. To explore the treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 3 Years ]
    • Number of participants with treatment-related adverse events as assessed by CTCAE v5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. histologically confirmed locally advanced or metastatic gastroenteropancreatic poorly differentiated neuroendocrine carcinoma.
  2. patients either are chemotherapy-naive or had received adjuvant chemotherapy > 6 months before recurrence.
  3. at least one measurable lesion according to the RECIST version 1.1..
  4. patients were aged 20 to 80 years with ECOG performance status of 0 to 1.
  5. patients had a life expectancy ≥ 3 months.
  6. patients had adequate renal function with defined as serum creatinine ≤ 2 times the upper limit of normal (ULN) or eGFR (calculated Ccr) ≥ 45 mL/min.
  7. patients had adequate hepatic function, defined as total bilirubin ≤ 1.5 times the ULN and alanine aminotransferase ≤ 2.5 the ULN and ≤ 5 times the ULN within the setting of liver metastases.
  8. patients had adequate bone marrow function, defined as an absolute neutrophil count ≥ 1500/mm3, platelet count ≥ 100,000/mm3, and hemoglobin ≥ 9 g/dL.
  9. Normal ECG or abnormal ECG without any clinical significantly findings.
  10. Able to understand and sign an informed consent (or have a legal representative who is able to do so).

Exclusion Criteria:

  1. a history of palliative chemotherapy or disease recurrence < 6 months from the time of last adjuvant chemotherapy and/or radiotherapy.
  2. known hypersensitivity to liposome product, irinotecan or carboplatin.
  3. receipt of major surgery within the past 4 weeks before study enrollment.
  4. With clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion or diarrhea > grade 2.
  5. concurrent severe infection with intravenous systemic antibiotics treatment.
  6. severe, uncontrolled medical condition including severe liver disease, heart disease, uncontrolled diabetes or hypertension, or pulmonary disease.
  7. another previous malignancy diagnosed within the past 5 years except for nonmelanoma skin cancer or stage I cervical cancer.
  8. active CNS metastasis defined by clinical symptoms, cerebral edema, steroid or anti-convulsant requirement, or progressive growth. Patients with a history of CNS metastasis or cord compression are allowed in the study if they have been treated and are clinically stable.
  9. psychiatric illness or social situation that would preclude study compliance
  10. women with pregnant or breast feeding (a urine pregnancy test must be performed on all patients who are of childbearing potential before entering the study, and the result must be negative).

Information from the National Library of Medicine

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): NCT05385861


Contacts
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Contact: Bor-Rong Chen 886-2-26534401 ext 25162 brong@nhri.edu.tw
Contact: Nai-Jung Chiang njchiang@nhri.edu.tw

Locations
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Taiwan
Chang-Gung Memorial Hospital, Kaohsiung
Kaohsiung, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, Taiwan
Chang Gung Memorial Hospital (Lin-Kou),
Linkou, Taiwan
China Medical University Hospital
Taichung, Taiwan
National Cheng-Kung University Hospital
Tainan, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Sponsors and Collaborators
National Health Research Institutes, Taiwan
Taipei Veterans General Hospital, Taiwan
Chang Gung Memorial Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Investigators
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Study Director: Tsang-Wu Liu Taiwan Cooperative Oncology Group, NHRI
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Responsible Party: National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier: NCT05385861    
Other Study ID Numbers: T2222
First Posted: May 23, 2022    Key Record Dates
Last Update Posted: May 23, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carboplatin
Irinotecan
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action