Description:
A Randomized, Open Label Phase 3 Study of Irinotecan Liposome Injection (ONIVYDE®) versus
Topotecan in Patients with Small Cell Lung Cancer Who Have Progressed on or after
Platinum-based First-Line Therapy
The study will be conducted in two parts:
1. Dose determination of irinotecan liposome injection
2. A randomized, efficacy study of irinotecan liposome injection versus topotecan
Title
- Brief Title: Study of Irinotecan Liposome Injection (ONIVYDE®) in Patients With Small Cell Lung Cancer
- Official Title: RESILIENT: A Randomized, Open Label Phase 3 Study of Irinotecan Liposome Injection (ONIVYDE®) Versus Topotecan in Patients With Small Cell Lung Cancer Who Have Progressed on or After Platinum-based First-Line Therapy
Clinical Trial IDs
- ORG STUDY ID:
MM-398-01-03-04
- SECONDARY ID:
2017-004261-26
- NCT ID:
NCT03088813
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Irinotecan liposome injection | ONIVYDE® | Experimental Arm |
Topotecan | | Control Arm |
Purpose
A Randomized, Open Label Phase 3 Study of Irinotecan Liposome Injection (ONIVYDE®) versus
Topotecan in Patients with Small Cell Lung Cancer Who Have Progressed on or after
Platinum-based First-Line Therapy
The study will be conducted in two parts:
1. Dose determination of irinotecan liposome injection
2. A randomized, efficacy study of irinotecan liposome injection versus topotecan
Detailed Description
The study will be conducted in two parts:
Part 1: Open-label dose-finding study of irinotecan liposome injection. 30 patients were
enrolled.
Part 1 Primary Objectives:
- Describe the safety and tolerability of irinotecan liposome injection monotherapy
administered every 2 weeks
- Determine the optimal irinotecan liposome injection monotherapy dose for Part 2 of this
study
Part 2: A randomized, efficacy study of irinotecan liposome injection versus IV topotecan.
Approximately 450 patients will be enrolled in part 2.
Part 2 objectives: Detailed in the Primary & Secondary outcome measure sections.
Trial Arms
Name | Type | Description | Interventions |
---|
Experimental Arm | Experimental | Irinotecan liposome injection | - Irinotecan liposome injection
|
Control Arm | Active Comparator | Topotecan | |
Eligibility Criteria
Inclusion Criteria:
- At least 18 years of age.
- Able to understand and provide an informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy >12 weeks
- Histopathologically or cytologically confirmed small cell lung cancer
- Evaluable disease as defined by RECIST Version 1.1 guidelines (patients with non
measurable lesions only are eligible).
- Radiologically confirmed progression on or after first-line platinum based
chemotherapy (carboplatin or cisplatin), immunotherapy, or chemo-radiation including
platinum-based chemotherapy for treatment of limited or extensive stage Small Cell
Lung Cancer (SCLC).
- Recovered from the effects of any prior chemotherapy, surgery, radiotherapy or other
anti-neoplastic therapy (recovered to Grade 1 or better, with the exception of
alopecia).
- Adequate bone marrow reserves
- Adequate hepatic function Adequate renal function
- Electrocardiogram during the Screening period without any clinically significant
findings, per investigator's assessment
- Patients with certain types of asymptomatic CNS metastases that meet ALL the following
criteria are eligible.
1. Patients with asymptomatic CNS metastases prior to enrollment
2. Prior radiation for CNS metastatic disease is completed ≥2 weeks prior to
enrollment
3. CNS metastases that are stable or have decreased according to the post radiation
follow-up scan that is conducted at least 4 weeks after completion of radiation
treatment for CNS lesion.
4. Patients have discontinued corticosteroids or are on stable low-dose steroids
(prednisone or equivalent 10 mg daily or less) for at least 1 week after
completion of radiation for CNS lesion prior to enrollment.
Exclusion Criteria
- Any medical or social condition deemed by the Investigator to be likely to interfere
with a patient's ability to sign informed consent, cooperate and participate in the
study, or interfere with the interpretation of the results
- Pregnant or breast feeding;
- Patients with large cell neuroendocrine lung carcinoma.
- Patients who have received prior topoisomerase I inhibitor treatment, retreatment with
e platinum-based regimen, antibody-drug conjugates or molecular targeted agents, more
than one line of immunotherapy, or any other additional regimen of prior cytotoxic
chemotherapy.
- Patients with the symptomatic Central Nervous System (CNS) metastasis and/or who have
developed new or progressive brain metastasis following prophylactic and/or
therapeutic cranial radiation (whole brain stereotactic radiation).
- Patients with carcinomatous meningitis.
- Unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week or
strong CYP3A4 inducers at least 2 weeks prior to receiving the first dose of
irinotecan liposome injection.
- Have a previous or concurrent cancer that is distinct in primary (non-pulmonary) site
or SCLC histology
- Investigational therapy administered within 4 weeks, or within a time interval less
than at least 5 half-lives of the investigational agent, whichever is less, prior to
the first scheduled day of dosing in this study.
- Severe cardiovascular and pulmonary diseases
- New York Heart Association Class III or IV congestive heart failure, ventricular
arrhythmias, or uncontrolled blood pressure.
- Active infection
- Known hypersensitivity to any of the components of irinotecan liposome injection,
other liposomal products, or topotecan.
- Clinically significant gastrointestinal disorder including hepatic disorders,
bleeding, inflammation, occlusion, or diarrhea > grade 1.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall survival (OS) |
Time Frame: | 40 months |
Safety Issue: | |
Description: | Overall survival is defined as the time from randomization to date of death. The primary hypothesis will test whether OS is increased in patients treated with irinotecan liposome injection |
Secondary Outcome Measures
Measure: | Progression-free survival |
Time Frame: | 40 months |
Safety Issue: | |
Description: | Progression-free survival is the time from randomization to the first documented objective disease progression (PD) using RECIST v1.1 or death due to any cause, whichever occurs first |
Measure: | Objective Response |
Time Frame: | 40 months |
Safety Issue: | |
Description: | Objective response is defined as the time from randomization to date of progression or death. Objective response rate (ORR) is the proportion of patients who achieve partial response or complete response according to RECIST v1.1 guidelines |
Measure: | Proportion of Patients with Symptom Improvement |
Time Frame: | Randomization to 30 Days after permanent treatment termination |
Safety Issue: | |
Description: | Patient-reported EORTC-QLQ symptom scales for cough, dyspnea, and fatigue |
Measure: | Incidence of treatment-emergent adverse events, serious adverse events and laboratory abnormalities |
Time Frame: | Enrollment to 30 days after permanent treatment termination |
Safety Issue: | |
Description: | Safety analyses (adverse events and laboratory analyses) will be performed using the safety population, defined as all patients receiving any study drug. |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Ipsen |
Last Updated
October 23, 2020