Study of Irinotecan Liposome Injection (ONIVYDE®) in Patients With Small Cell Lung Cancer

NCT03088813 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MM-398-01-03-042017-004261-26
• Study Type: interventional
• Target: 491
• Locations: 18 countries
• Sites: 118

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. 1.Dose determination of irinotecan liposome injection
2. 2.A randomized, efficacy study of irinotecan liposome injection versus topotecan

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant following or during exposure to a study treatment, whether or not causally related to the study treatment. An undesirable medical condition could be symptoms, signs or abnormal results of an investigation. An SAE was any AE that: resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; resulted in congenital anomaly or birth defect; or was medically important. A TEAE was any AE that occurred or worsened on or after the day of first dose of study treatment and within 30 days after discontinuation of study treatment.

  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

• Part 1: Number of Participants With Dose-Limiting Toxicities (DLT)

  A TEAE was considered as DLT if it occurred during the safety evaluation period (i.e. first 28 days of treatment or 14 days after the second dose of study treatment if there was a treatment delay due to non-DLT related reasons) and were deemed related to the study treatment by the investigator. The determination of whether an Adverse Event was considered a Dose Limiting Toxicity was made by the Safety Review Committee (SRC) comprising the Part 1 Investigators and the Medical Monitor(s) of the Sponsor.

  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

• Part 2: Overall Survival (OS)

  The OS was defined as the time from randomization date to the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. The OS was calculated using Kaplan-Meier technique. Following end of treatment participant and/or family was contacted by telephone every month to assess vital status.

  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 (9)

• Part 1: Objective Response Rate (ORR)

  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

• Part 1: Progression-Free Survival (PFS)

  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

• Part 1: OS

  From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days)

• Part 2: PFS

  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

• Part 2: ORR

  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

Study Arms (4)

Part 1: Experimental Arm, dose level 1

EXPERIMENTAL

Irinotecan liposome injection

Drug: Irinotecan liposome injection

Part 1: Experimental Arm, dose level 2

EXPERIMENTAL

Irinotecan liposome injection

Drug: Irinotecan liposome injection

Part 2: Experimental Arm

EXPERIMENTAL

Irinotecan liposome injection

Drug: Irinotecan liposome injection

Part 2: Control Arm

ACTIVE COMPARATOR

Topotecan

Drug: Topotecan

Interventions

Irinotecan liposome injection DRUG

IV

Also known as: ONIVYDE®

Part 1: Experimental Arm, dose level 1; Part 1: Experimental Arm, dose level 2; Part 2: Experimental Arm

Topotecan DRUG

IV

Part 2: Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients with asymptomatic CNS metastases prior to enrollment
• Prior radiation for CNS metastatic disease is completed ≥4 weeks prior to enrollment

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (118)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists (South Region)

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

Cancer Treatment Centers of America-Georgia

Newnan, Georgia, 30265, United States

Location

Illinois Cancer Care, PC

Peoria, Illinois, 61615, United States

Location

Southern Maine Health Care

Biddeford, Maine, 04005, United States

Location

University of Maryland Medical Group

Baltimore, Maryland, 21201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Sparrow Regional Cancer Center

Lansing, Michigan, 48219, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

North Shore Hematology Oncology Associates, PC

East Setauket, New York, 11733, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Tri County Hematology & Oncology Associates, Inc

Massillon, Ohio, 44646, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Charleston Hematology Oncology Associates, PA

Charleston, South Carolina, 29414, United States

Location

Greenville Hospital System University Medical Center

Greenville, South Carolina, 29605, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MultiCare Health System Institute for Research and Innovation

Spokane, Washington, 99204, United States

Location

Summit Cancer Treatment Center

Spokane, Washington, 99208, United States

Location

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

South West Healthcare

Warrnambool, Victoria, 3280, Australia

Location

Southern Medical Day Care Centre

Wollongong, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Australia

Location

AZ Klina

Brasschaat, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Centre Hospitalier de l'Ardenne

Libramont, Belgium

Location

AZ Sint-Maarten

Mechelen, Belgium

Location

Hospital de Cancer de Barretos, Fundacoa Pio X II

Barretos, Brazil

Location

Hospital de Caridade de Ijuí

Ijuí, Brazil

Location

Oncobio Servicos de Saude

Nova Lima, Brazil

Location

HGB - Hospital Giovanni Battista - Mãe de Deus Center

Porto Alegre, Brazil

Location

Hospital Nossa Senhora da Conceição

Porto Alegre, Brazil

Location

INCA - Instituto Nacional de Câncer

Rio de Janeiro, Brazil

Location

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, Brazil

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

The First Affiliated Hospital of Bengbu Medical College

Bengbu, 233004, China

Location

The First Hospital of Jilin University

Changchun, 450008, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510080, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Tongji Hospital

Hubei, 430030, China

Location

Linyi Cancer Hospital

Linyi, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

CHU Brest - Hôpital Morvan

Brest, France

Location

Hôpital Nord - CHU Marseille

Marseille, France

Location

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, France

Location

Centre Hospitalier de Saint-Quentin

Saint-Quentin, 02321, France

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Evangelisches Krankenhaus Hamm GmbH

Hamm, 50063, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Pius-Hospital Oldenburg

Oldenburg, 26121, Germany

Location

Semmelweis Egyetem

Budapest, Hungary

Location

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza

Gyula, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, Hungary

Location

Tudogyogyintezet Torokbalint

Törökbálint, Hungary

Location

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, Hungary

Location

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine

Udine, Italy

Location

KO-MED Centra Kliniczne Biala Podlaska

Biała Podlaska, Poland

Location

Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością

Gdynia, Poland

Location

SP Zespol Gruzlicy i Chorob Pluc w Olsztynie

Olsztyn, Poland

Location

Przychodnia Med-Polonia Sp. z o.o.

Poznan, Poland

Location

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, Poland

Location

S.C Gral Medical S.R.L

Bucharest, Romania

Location

Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca

Cluj-Napoca, Romania

Location

S.C Medisprof S.R.L

Cluj-Napoca, Romania

Location

S.C Centrul de Oncologie Sf. Nectarie S.R.L

Craiova, Romania

Location

S.C Radiotherapy Center Cluj S.R.L

Floreşti, Romania

Location

Oncomed SRL

Timișoara, Romania

Location

SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"

Arkhangelsk, Russia

Location

"VitaMed" LLC

Moscow, Russia

Location

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, Russia

Location

SBHI of Kaluga Region "Kaluga regional clinical oncology dispensary"

Saint Petersburg, 197022, Russia

Location

SPb SBIH "City Clinical Oncological Dispensary"

Saint Petersburg, Russia

Location

SBIH of Yaroslavl region "Regional Clinical Oncological Hospital"

Yaroslavl, Russia

Location

Clinical Center "Bezanijska kosa"

Belgrade, Serbia

Location

Clinical Center Kragujevac

Belgrade, Serbia

Location

Oncomed System

Belgrade, Serbia

Location

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, Serbia

Location

General Hospital Uzice

Užice, 31000, Serbia

Location

Chungbuk National University Hospital

Cheongju-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, South Korea

Location

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Changhua Christian Hospital

Changhua, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan District, 333, Taiwan

Location

Baskent University Adana Application and Research Center

Adana, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, Turkey (Türkiye)

Location

Istanbul Medeniyet Uni Goztepe Training&Res Hosp

Istanbul, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, Turkey (Türkiye)

Location

Inonu Uni. Med. Fac.

Malatya, Turkey (Türkiye)

Location

Namik Kemal University

Tekirdağ, Turkey (Türkiye)

Location

CI Chernivtsi RC Oncological Dispensary

Chernivtsi, Ukraine

Location

CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU

Dnipro, Ukraine

Location

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, 61070, Ukraine

Location

Communal Enterprise Kremenchuk Regional Oncology Dispensary of Poltava Regional Council

Kremenchuk, 39617, Ukraine

Location

CI Kryvyi Rih Oncological Dispensary of DRC

Kryvyi Rih, Ukraine

Location

Treatment-Prevention Institution Volyn Regional Oncological Dispensary

Lutsk, Ukraine

Location

Odesa Regional Oncologic Dispensary

Odesa, Ukraine

Location

RCI Sumy Regional Clinical Oncological Dispensary

Sumy, Ukraine

Location

CCCH City Oncological Center SHEI Uzhgorod NU

Uzhhorod, 88000, Ukraine

Location

Medical Clinic Innovacia, LLC

Vyshhorod, 07352, Ukraine

Location

Related Publications (2)

• Spigel DR, Dowlati A, Chen Y, Navarro A, Yang JC, Stojanovic G, Jove M, Rich P, Andric ZG, Wu YL, Rudin CM, Chen H, Zhang L, Yeung S, Benzaghou F, Paz-Ares L, Bunn PA; RESILIENT Trial Investigators. RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 1;42(19):2317-2326. doi: 10.1200/JCO.23.02110. Epub 2024 Apr 22.

  PMID: 38648575 DERIVED

• 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.

  PMID: 35195913 DERIVED

Related Links

• Lay language results summary

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

irinotecan sucrosofate; Topotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen Bioscience, Inc.

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 23, 2017
• Study Start: April 25, 2018
• Primary Completion: February 8, 2022
• Study Completion: July 27, 2023
• Last Updated: February 19, 2025
• Results First Posted: October 17, 2023

Record last verified: 2025-02

Locations

BE (4); UA (10); US (22); RU (6); DE (4); IT (3); TW (5); RO (6); KR (4); FR (4); ES (8); HU (5); SE (5); TU (6); AU (4); CN (9); PL (5); BR (8)