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

NCT ID: NCT03088813

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 491 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-25
• Study Completion Date: 2023-07-27

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.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Experimental Arm, dose level 1

Irinotecan liposome injection

Group Type: EXPERIMENTAL

Irinotecan liposome injection

Intervention Type: DRUG

IV

Part 1: Experimental Arm, dose level 2

Irinotecan liposome injection

Group Type: EXPERIMENTAL

Irinotecan liposome injection

Intervention Type: DRUG

IV

Part 2: Experimental Arm

Irinotecan liposome injection

Group Type: EXPERIMENTAL

Irinotecan liposome injection

Intervention Type: DRUG

IV

Part 2: Control Arm

Topotecan

Group Type: ACTIVE_COMPARATOR

Topotecan

Intervention Type: DRUG

IV

Interventions

Irinotecan liposome injection

IV

Intervention Type: DRUG

Topotecan

IV

Intervention Type: DRUG

Other Intervention Names

ONIVYDE®

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

National Jewish Health

Denver, Colorado, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Florida Cancer Specialists (South Region)

Fort Myers, Florida, United States

Florida Cancer Specialists

St. Petersburg, Florida, United States

Northwest Georgia Oncology Centers

Marietta, Georgia, United States

Cancer Treatment Centers of America-Georgia

Newnan, Georgia, United States

Illinois Cancer Care, PC

Peoria, Illinois, United States

Southern Maine Health Care

Biddeford, Maine, United States

University of Maryland Medical Group

Baltimore, Maryland, United States

Henry Ford Hospital

Detroit, Michigan, United States

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Sparrow Regional Cancer Center

Lansing, Michigan, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

North Shore Hematology Oncology Associates, PC

East Setauket, New York, United States

Case Western Reserve University

Cleveland, Ohio, United States

Tri County Hematology & Oncology Associates, Inc

Massillon, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Charleston Hematology Oncology Associates, PA

Charleston, South Carolina, United States

Greenville Hospital System University Medical Center

Greenville, South Carolina, United States

Tennessee Oncology

Nashville, Tennessee, United States

MultiCare Health System Institute for Research and Innovation

Spokane, Washington, United States

Summit Cancer Treatment Center

Spokane, Washington, United States

Border Medical Oncology Research Unit

Albury, New South Wales, Australia

South West Healthcare

Warrnambool, Victoria, Australia

Southern Medical Day Care Centre

Wollongong, , Australia

Princess Alexandra Hospital

Woolloongabba, , Australia

AZ Klina

Brasschaat, , Belgium

UZ Leuven

Leuven, , Belgium

Centre Hospitalier de l'Ardenne

Libramont, , Belgium

AZ Sint-Maarten

Mechelen, , Belgium

Hospital de Cancer de Barretos, Fundacoa Pio X II

Barretos, , Brazil

Hospital de Caridade de Ijuí

Ijuí, , Brazil

Oncobio Servicos de Saude

Nova Lima, , Brazil

HGB - Hospital Giovanni Battista - Mãe de Deus Center

Porto Alegre, , Brazil

Hospital Nossa Senhora da Conceição

Porto Alegre, , Brazil

INCA - Instituto Nacional de Câncer

Rio de Janeiro, , Brazil

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, , Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, , Brazil

Beijing Cancer Hospital

Beijing, , China

The First Affiliated Hospital of Bengbu Medical College

Bengbu, , China

The First Hospital of Jilin University

Changchun, , China

West China Hospital, Sichuan University

Chengdu, , China

Guangdong Provincial People's Hospital

Guangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Tongji Hospital

Hubei, , China

Linyi Cancer Hospital

Linyi, , China

Henan Cancer Hospital

Zhengzhou, , China

CHU Brest - Hôpital Morvan

Brest, , France

Hôpital Nord - CHU Marseille

Marseille, , France

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, , France

Centre Hospitalier de Saint-Quentin

Saint-Quentin, , France

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Evangelisches Krankenhaus Hamm GmbH

Hamm, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Pius-Hospital Oldenburg

Oldenburg, , Germany

Semmelweis Egyetem

Budapest, , Hungary

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza

Gyula, , Hungary

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, , Hungary

Tudogyogyintezet Torokbalint

Törökbálint, , Hungary

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, , Hungary

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Azienda Sanitaria Universitaria Integrata di Udine

Udine, , Italy

KO-MED Centra Kliniczne Biala Podlaska

Biała Podlaska, , Poland

Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością

Gdynia, , Poland

SP Zespol Gruzlicy i Chorob Pluc w Olsztynie

Olsztyn, , Poland

Przychodnia Med-Polonia Sp. z o.o.

Poznan, , Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, , Poland

S.C Gral Medical S.R.L

Bucharest, , Romania

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

Cluj-Napoca, , Romania

S.C Medisprof S.R.L

Cluj-Napoca, , Romania

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

Craiova, , Romania

S.C Radiotherapy Center Cluj S.R.L

Floreşti, , Romania

Oncomed SRL

Timișoara, , Romania

SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"

Arkhangelsk, , Russia

"VitaMed" LLC

Moscow, , Russia

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, , Russia

SBHI of Kaluga Region "Kaluga regional clinical oncology dispensary"

Saint Petersburg, , Russia

SPb SBIH "City Clinical Oncological Dispensary"

Saint Petersburg, , Russia

SBIH of Yaroslavl region "Regional Clinical Oncological Hospital"

Yaroslavl, , Russia

Clinical Center "Bezanijska kosa"

Belgrade, , Serbia

Clinical Center Kragujevac

Belgrade, , Serbia

Oncomed System

Belgrade, , Serbia

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, , Serbia

General Hospital Uzice

Užice, , Serbia

Chungbuk National University Hospital

Cheongju-si, , South Korea

Asan Medical Center

Seoul, , South Korea

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

Seoul, , South Korea

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

Suwon, , South Korea

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Changhua Christian Hospital

Changhua, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan District, , Taiwan

Baskent University Adana Application and Research Center

Adana, , Turkey (Türkiye)

Trakya University Medical Faculty

Edirne, , Turkey (Türkiye)

Istanbul Medeniyet Uni Goztepe Training&Res Hosp

Istanbul, , Turkey (Türkiye)

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Inonu Uni. Med. Fac.

Malatya, , Turkey (Türkiye)

Namik Kemal University

Tekirdağ, , Turkey (Türkiye)

CI Chernivtsi RC Oncological Dispensary

Chernivtsi, , Ukraine

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

Dnipro, , Ukraine

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, , Ukraine

Communal Enterprise Kremenchuk Regional Oncology Dispensary of Poltava Regional Council

Kremenchuk, , Ukraine

CI Kryvyi Rih Oncological Dispensary of DRC

Kryvyi Rih, , Ukraine

Treatment-Prevention Institution Volyn Regional Oncological Dispensary

Lutsk, , Ukraine

Odesa Regional Oncologic Dispensary

Odesa, , Ukraine

RCI Sumy Regional Clinical Oncological Dispensary

Sumy, , Ukraine

CCCH City Oncological Center SHEI Uzhgorod NU

Uzhhorod, , Ukraine

Medical Clinic Innovacia, LLC

Vyshhorod, , Ukraine

Countries

United States; Australia; Belgium; Brazil; China; France; Germany; Hungary; Italy; Poland; Romania; Russia; Serbia; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine

References

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.

Reference Type: DERIVED

PMID: 38648575 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35195913 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.ipsen.com/websites/ipsen_com_v2/wp-content/uploads/2024/11/08172330/MM-398-01-03-04-lay-results-summary.pdf

Lay language results summary

Other Identifiers

2017-004261-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MM-398-01-03-04

Identifier Type: -

Identifier Source: org_study_id