Clinical trial NCT03088813: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Small Cell Lung Cancer
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2017-03-23
Enrollment: 491
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: The study was conducted in two parts:

Part 1: Open-label dose-finding study of irinotecan liposome injection. 30 patients were planned to be 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 intravenous (IV) topotecan.

Approximately 450 patients were planned to be enrolled in part 2.

Part 2 objectives: To compare overall survival following treatment with irinotecan liposome injection with overall survival following treatment with IV 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), 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.

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.

Primary outcomes:
measure: Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: 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
measure: Part 1: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: 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
measure: Part 2: Overall Survival (OS)
timeFrame: 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 outcomes:
measure: Part 1: Objective Response Rate (ORR)
timeFrame: 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
measure: Part 1: Progression-Free Survival (PFS)
timeFrame: 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
measure: Part 1: OS
timeFrame: From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days)
measure: Part 2: PFS
timeFrame: 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
measure: Part 2: ORR
timeFrame: 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
measure: Part 2: Median Duration of Response (DoR)
timeFrame: 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
measure: Part 2: Median Time to Objective Response (OR)
timeFrame: 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
measure: 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
timeFrame: Baseline (Day 1) and Week 12
measure: Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12
timeFrame: Baseline (Day 1) and Week 12
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists (South Region)
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers
state: Georgia
city: Newnan
country: United States
facility: Cancer Treatment Centers of America-Georgia
state: Georgia
city: Peoria
country: United States
facility: Illinois Cancer Care, PC
state: Illinois
city: Biddeford
country: United States
facility: Southern Maine Health Care
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Group
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates, PC
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Massillon
country: United States
facility: Tri County Hematology & Oncology Associates, Inc
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates, PA
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Center
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Spokane
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Spokane
country: United States
facility: Summit Cancer Treatment Center
state: Washington
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Warrnambool
country: Australia
facility: South West Healthcare
state: Victoria
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Leuven
country: Belgium
facility: UZ Leuven
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos, Fundacoa Pio X II
city: Ijuí
country: Brazil
facility: Hospital de Caridade de Ijuí
city: Nova Lima
country: Brazil
facility: Oncobio Servicos de Saude
city: Porto Alegre
country: Brazil
facility: HGB - Hospital Giovanni Battista - Mãe de Deus Center
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição
city: Rio De Janeiro
country: Brazil
facility: INCA - Instituto Nacional de Câncer
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: São José Do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Hubei
country: China
facility: Tongji Hospital
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Brest
country: France
facility: CHU Brest - Hôpital Morvan
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Saint-Quentin
country: France
facility: Centre Hospitalier de Saint-Quentin
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm GmbH
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
city: Törökbálint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Biała Podlaska
country: Poland
facility: KO-MED Centra Kliniczne Biala Podlaska
city: Gdynia
country: Poland
facility: Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością
city: Olsztyn
country: Poland
facility: SP Zespol Gruzlicy i Chorob Pluc w Olsztynie
city: Poznań
country: Poland
facility: Przychodnia Med-Polonia Sp. z o.o.
city: Poznań
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
city: Bucuresti
country: Romania
facility: S.C Gral Medical S.R.L
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
city: Cluj-Napoca
country: Romania
facility: S.C Medisprof S.R.L
city: Craiova
country: Romania
facility: S.C Centrul de Oncologie Sf. Nectarie S.R.L
city: Floreşti
country: Romania
facility: S.C Radiotherapy Center Cluj S.R.L
city: Timişoara
country: Romania
facility: Oncomed SRL
city: Arkhangel'sk
country: Russian Federation
facility: SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
city: Moscow
country: Russian Federation
facility: "VitaMed" LLC
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: SBHI of Kaluga Region "Kaluga regional clinical oncology dispensary"
city: Saint Petersburg
country: Russian Federation
facility: SPb SBIH "City Clinical Oncological Dispensary"
city: Yaroslavl
country: Russian Federation
facility: SBIH of Yaroslavl region "Regional Clinical Oncological Hospital"
city: Belgrade
country: Serbia
facility: Clinical Center "Bezanijska kosa"
city: Belgrade
country: Serbia
facility: Oncomed System
city: Belgrad
country: Serbia
facility: Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Užice
country: Serbia
facility: General Hospital Uzice
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Adana
country: Turkey
facility: Baskent University Adana Application and Research Center
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet Uni Goztepe Training&Res Hosp
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
city: Malatya
country: Turkey
facility: Inonu Uni. Med. Fac.
city: Tekirdağ
country: Turkey
facility: Namik Kemal University
city: Chernivtsi
country: Ukraine
facility: CI Chernivtsi RC Oncological Dispensary
city: Dnipro
country: Ukraine
facility: CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
city: Kharkiv
country: Ukraine
facility: Communal Non-profit Enterprise Regional Center of Oncology
city: Kremenchuk
country: Ukraine
facility: Communal Enterprise Kremenchuk Regional Oncology Dispensary of Poltava Regional Council
city: Kryvyi Rih
country: Ukraine
facility: CI Kryvyi Rih Oncological Dispensary of DRC
city: Luts'k
country: Ukraine
facility: Treatment-Prevention Institution Volyn Regional Oncological Dispensary
city: Odesa
country: Ukraine
facility: Odesa Regional Oncologic Dispensary
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Uzhgorod
country: Ukraine
facility: CCCH City Oncological Center SHEI Uzhgorod NU
city: Vyshhorod
country: Ukraine
facility: Medical Clinic Innovacia, LLC
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.