Study of Irinotecan Liposome Injection (ONIVYDE®) in Patients With Small Cell Lung Cancer
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03088813
- Lead Sponsor
- Ipsen
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 491
-
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).
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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
- 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.
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Experimental Arm, dose level 1 Irinotecan liposome injection Irinotecan liposome injection Part 1: Experimental Arm, dose level 2 Irinotecan liposome injection Irinotecan liposome injection Part 2: Control Arm Topotecan Topotecan Part 2: Experimental Arm Irinotecan liposome injection Irinotecan liposome injection
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Dose-Limiting Toxicities (DLT) 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 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.
Part 2: Overall Survival (OS) 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) 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.
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) 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 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.
- Secondary Outcome Measures
Name Time Method 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 The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) recorded from date of first dose of study treatment until documented PD or death. ORR analysis was based on BOR using RECIST v1.1 per investigator assessment. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. Per protocol, participants had computed tomography (CT)-scans and brain magnetic resonance imaging (MRI) every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Part 1: OS From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days) The OS was defined as the time from first dose of study treatment 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.
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 The ORR was defined as percentage of participants with a BOR characterized as either a CR or PR, recorded from randomization until documented PD or death relative to the total number of participants. ORR analysis was based on BOR assessed by BICR using RECIST v1.1. Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Part 2: Median Duration of Response (DoR) 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 The DoR was defined as time from the first documented objective response (CR or PR, whichever was earlier) to the date of first documented PD or death due to any cause. The DoR analysis was based on BOR assessed by BICR using RECIST v1.1. Per RECIST v1.1, CR is disappearance of all target lesions and PR is \>=30% decrease in the sum of the longest diameter of target lesions. The DoR was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12 Baseline (Day 1) and Week 12 The EORTC QLQ-LC13 is a lung cancer specific module used in conjunction with EORTC QLQ-C30 and covers typical symptoms of lung cancer (cough, pain, dyspnea, sore mouth, peripheral neuropathy, hair loss). Score ranges from 0-100 scale and a high score represents a high level of symptomatology/problems/worse QoL. Baseline was defined as the last non-missing measurement taken prior to reference start date. Change from baseline in cough scale was calculated regardless of premature study treatment discontinuation. Participants completed these questionnaires on an electronic tablet every 6 weeks during treatment and it was continued until PD or commencement of new anti-neoplastic therapy.
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 The PFS was defined as time from first dose of study treatment to the first documented objective PD using RECIST v1.1 or death due to any cause, whichever occurs first. Per RECIST 1.1, progression is defined as at least 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
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 The PFS was defined as time from randomization to first documented objective PD using RECIST 1.1 (or response assessment in neuro-oncology brain metastases \[RANO-BM\] criteria for central nervous system \[CNS\] lesions) as assessed by blinded independent central review (BICR) or death due to any cause, whichever occurred first. Per RECIST 1.1, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS was calculated using Kaplan-Meier technique. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
Part 2: Median Time to Objective Response (OR) 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 Time to OR as per RECIST v1.1 criteria according to BICR was defined as time from the date of randomization to the date of first documented objective tumor response (CR or PR, whichever was first). Per RECIST v1.1, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesion. Participants with a new anti-cancer therapy prior to OR were censored at the last tumor assessment prior to new anti-cancer therapy. Per protocol, participants had CT-scans and brain MRI every 6 weeks to measure tumor lesion size. This was continued throughout treatment until PD or commencement of new anti-neoplastic therapy.
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 Baseline (Day 1) and Week 12 The EORTC QLQ-LC13 is a lung cancer specific module used in conjunction with EORTC QLQ-C30 and covers typical symptoms of lung cancer (cough, pain, dyspnea, sore mouth, peripheral neuropathy, hair loss). Scores range from 0-100 and a high score represents a high level of symptomatology/problems/worse QoL. Baseline was defined as the last non-missing measurement taken prior to reference start date. Change from baseline in dyspnea scale was calculated regardless of premature study treatment discontinuation. Participants completed these questionnaires on an electronic tablet every 6 weeks during treatment and it was continued until PD or commencement of new anti-neoplastic therapy.
Trial Locations
- Locations (118)
Florida Cancer Specialists (South Region)
🇺🇸Fort Myers, Florida, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
North Shore Hematology Oncology Associates, PC
🇺🇸East Setauket, New York, United States
Tri County Hematology & Oncology Associates, Inc
🇺🇸Massillon, Ohio, United States
Hospital de Caridade de Ijuí
🇧🇷Ijuí, Brazil
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
General Hospital Uzice
🇷🇸Užice, Serbia
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan, Taiwan
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
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
University of Maryland Medical Group
🇺🇸Baltimore, Maryland, United States
Cancer & Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Sparrow Regional Cancer Center
🇺🇸Lansing, Michigan, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Summit Cancer Treatment Center
🇺🇸Spokane, Washington, United States
MultiCare Health System Institute for Research and Innovation
🇺🇸Spokane, Washington, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Border Medical Oncology Research Unit
🇦🇺Albury, New South Wales, Australia
Southern Medical Day Care Centre
🇦🇺Wollongong, Australia
Centre Hospitalier de l'Ardenne
🇧🇪Libramont, Belgium
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
Beijing Cancer Hospital
🇨🇳Beijing, China
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷São José Do Rio Preto, Brazil
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
Henan Cancer Hospital
🇨🇳Zhengzhou, China
Linyi Cancer Hospital
🇨🇳Linyi, China
Tongji Hospital
🇨🇳Hubei, China
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Pius-Hospital Oldenburg
🇩🇪Oldenburg, Germany
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
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
KO-MED Centra Kliniczne Biala Podlaska
🇵🇱Biała Podlaska, Poland
SP Zespol Gruzlicy i Chorob Pluc w Olsztynie
🇵🇱Olsztyn, Poland
Przychodnia Med-Polonia Sp. z o.o.
🇵🇱Poznań, Poland
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
🇵🇱Poznań, Poland
S.C Gral Medical S.R.L
🇷🇴Bucuresti, 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
SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
🇷🇺Arkhangel'sk, Russian Federation
Oncomed SRL
🇷🇴Timişoara, Romania
SBHI of Kaluga Region "Kaluga regional clinical oncology dispensary"
🇷🇺Saint Petersburg, Russian Federation
SPb SBIH "City Clinical Oncological Dispensary"
🇷🇺Saint Petersburg, Russian Federation
Clinical Center "Bezanijska kosa"
🇷🇸Belgrade, Serbia
SBIH of Yaroslavl region "Regional Clinical Oncological Hospital"
🇷🇺Yaroslavl, Russian Federation
Clinical Center Kragujevac
🇷🇸Belgrad, Serbia
Institute for Pulmonary Diseases of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Inonu Uni. Med. Fac.
🇹🇷Malatya, Turkey
CI Chernivtsi RC Oncological Dispensary
🇺🇦Chernivtsi, Ukraine
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Istanbul Medeniyet Uni Goztepe Training&Res Hosp
🇹🇷Istanbul, Turkey
Namik Kemal University
🇹🇷Tekirdağ, Turkey
Communal Enterprise Kremenchuk Regional Oncology Dispensary of Poltava Regional Council
🇺🇦Kremenchuk, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
🇺🇦Sumy, Ukraine
CCCH City Oncological Center SHEI Uzhgorod NU
🇺🇦Uzhgorod, Ukraine
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
AZ Sint-Maarten
🇧🇪Mechelen, Belgium
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸L'Hospitalet De Llobregat, Barcelona, Spain
Greenville Hospital System University Medical Center
🇺🇸Greenville, South Carolina, United States
Southern Maine Health Care
🇺🇸Biddeford, Maine, United States
"VitaMed" LLC
🇷🇺Moscow, Russian Federation
Baskent University Adana Application and Research Center
🇹🇷Adana, Turkey
CHU Brest - Hôpital Morvan
🇫🇷Brest, France
Institut de Cancérologie de la Loire
🇫🇷Saint-Priest-en-Jarez, France
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
🇭🇺Gyula, Hungary
Azienda Sanitaria Universitaria Integrata di Udine
🇮🇹Udine, Italy
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon, Korea, Republic of
BHI of Omsk region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
Treatment-Prevention Institution Volyn Regional Oncological Dispensary
🇺🇦Luts'k, Ukraine
Odesa Regional Oncologic Dispensary
🇺🇦Odesa, Ukraine
South West Healthcare
🇦🇺Warrnambool, Victoria, Australia
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Hospital de Cancer de Barretos, Fundacoa Pio X II
🇧🇷Barretos, Brazil
Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
Oncomed System
🇷🇸Belgrade, Serbia
CI Kryvyi Rih Oncological Dispensary of DRC
🇺🇦Kryvyi Rih, Ukraine
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
AZ Klina
🇧🇪Brasschaat, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Hôpital Nord - CHU Marseille
🇫🇷Marseille, France
Centre Hospitalier de Saint-Quentin
🇫🇷Saint-Quentin, France
Evangelisches Krankenhaus Hamm GmbH
🇩🇪Hamm, Germany
Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością
🇵🇱Gdynia, Poland
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
Medical Clinic Innovacia, LLC
🇺🇦Vyshhorod, Ukraine
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
National Jewish Health
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Charleston Hematology Oncology Associates, PA
🇺🇸Charleston, South Carolina, United States