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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03088813




Registration number
NCT03088813
Ethics application status
Date submitted
9/03/2017
Date registered
23/03/2017
Date last updated
17/07/2024

Titles & IDs
Public title
Study of Irinotecan Liposome Injection (ONIVYDE®) in Patients With Small Cell Lung Cancer
Scientific 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
Secondary ID [1] 0 0
2017-004261-26
Secondary ID [2] 0 0
MM-398-01-03-04
Universal Trial Number (UTN)
Trial acronym
RESILIENT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Irinotecan liposome injection
Treatment: Drugs - Topotecan

Experimental: Part 1: Experimental Arm, dose level 1 - Irinotecan liposome injection

Experimental: Part 1: Experimental Arm, dose level 2 - Irinotecan liposome injection

Experimental: Part 2: Experimental Arm - Irinotecan liposome injection

Active comparator: Part 2: Control Arm - Topotecan


Treatment: Drugs: Irinotecan liposome injection
IV

Treatment: Drugs: Topotecan
IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
Timepoint [1] 0 0
The TEAEs were reported from the time of first study treatment administration (Day 1) up to 30 days after the date of last study treatment administration, approximately 680 days
Primary outcome [2] 0 0
Part 1: Number of Participants With Dose-Limiting Toxicities (DLT)
Timepoint [2] 0 0
From the start of the first study treatment administration (Day 1) up to 14 days after the second dose of study treatment administration, a maximum of 42 days
Primary outcome [3] 0 0
Part 2: Overall Survival (OS)
Timepoint [3] 0 0
From date of randomization (within 7 days before start of study treatment) until death. Assessed up to Part 2 primary analysis DCO date of 08 February 2022 (approximately 900 days)
Secondary outcome [1] 0 0
Part 1: Objective Response Rate (ORR)
Timepoint [1] 0 0
RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days
Secondary outcome [2] 0 0
Part 1: Progression-Free Survival (PFS)
Timepoint [2] 0 0
RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days
Secondary outcome [3] 0 0
Part 1: OS
Timepoint [3] 0 0
From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days)
Secondary outcome [4] 0 0
Part 2: PFS
Timepoint [4] 0 0
RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Secondary outcome [5] 0 0
Part 2: ORR
Timepoint [5] 0 0
RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Secondary outcome [6] 0 0
Part 2: Median Duration of Response (DoR)
Timepoint [6] 0 0
RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Secondary outcome [7] 0 0
Part 2: Median Time to Objective Response (OR)
Timepoint [7] 0 0
RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days
Secondary outcome [8] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)/Lung Cancer Supplement (LC13) Dyspnea Scale at Week 12
Timepoint [8] 0 0
Baseline (Day 1) and Week 12
Secondary outcome [9] 0 0
Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12
Timepoint [9] 0 0
Baseline (Day 1) and Week 12

Eligibility
Key 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), or chemo-radiation including platinum-based chemotherapy for treatment of limited or extensive stage Small Cell Lung Cancer (SCLC). In addition to platinum-based regimen, one line of immunotherapy as monotherapy or in combination, in first or in second line setting is allowed.
* 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, peripheral neuropathy, or ototoxicity).
* 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 =4 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 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 within 3 months 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/07/2023
Sample size
Target
Accrual to date
Final
491
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
South West Healthcare - Warrnambool
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
3280 - Warrnambool
Recruitment postcode(s) [3] 0 0
- Wollongong
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
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United States of America
State/province [2] 0 0
Florida
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Georgia
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Illinois
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Maine
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Maryland
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Michigan
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New York
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Ohio
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Oklahoma
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South Carolina
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Tennessee
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Washington
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Belgium
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Brasschaat
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Leuven
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Libramont
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Belgium
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Mechelen
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Ijuí
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Santo André
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China
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Beijing
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China
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China
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Chengdu
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China
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Hangzhou
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China
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Hubei
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China
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Linyi
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China
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Zhengzhou
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Belgrad
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Barcelona
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Istanbul
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Ukraine
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Chernivtsi
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Dnipro
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Kharkiv
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Kremenchuk
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Kryvyi Rih
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Luts'k
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Odesa
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Sumy
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Uzhgorod
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Ukraine
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Vyshhorod

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ipsen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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 was conducted in two parts:

1. Dose determination of irinotecan liposome injection
2. A randomized, efficacy study of irinotecan liposome injection versus topotecan
Trial website
https://clinicaltrials.gov/study/NCT03088813
Trial related presentations / publications
Paz-Ares L, Spigel DR, Chen Y, Jove M, Juan-Vidal O, Rich P, Hayes T, Calderon VG, Caro RB, Navarro A, Dowlati A, Zhang B, Moore Y, Yao X, Kokhreidze J, Ponce S, Bunn PA. RESILIENT part 1: a phase 2 dose-exploration and dose-expansion study of second-line liposomal irinotecan in adults with small cell lung cancer. Cancer. 2022 May 1;128(9):1801-1811. doi: 10.1002/cncr.34123. Epub 2022 Feb 23.
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03088813