Clinical Trials /

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

NCT03088813

Description:

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 will be conducted in two parts: 1. Dose determination of irinotecan liposome injection 2. A randomized, efficacy study of irinotecan liposome injection versus topotecan

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MM-398-01-03-04
  • SECONDARY ID: 2017-004261-26
  • NCT ID: NCT03088813

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Irinotecan liposome injectionONIVYDE®Experimental Arm
TopotecanControl Arm

Purpose

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 will be 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 will be conducted in two parts:

      Part 1: Open-label dose-finding study of irinotecan liposome injection. 30 patients were
      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 IV topotecan.

      Approximately 450 patients will be enrolled in part 2.

      Part 2 objectives: Detailed in the Primary & Secondary outcome measure sections.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental ArmExperimentalIrinotecan liposome injection
  • Irinotecan liposome injection
Control ArmActive ComparatorTopotecan
  • 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), immunotherapy, or chemo-radiation including
             platinum-based chemotherapy for treatment of limited or extensive stage Small Cell
             Lung Cancer (SCLC).

          -  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).

          -  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 ≥2 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
             e 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS)
Time Frame:40 months
Safety Issue:
Description:Overall survival is defined as the time from randomization to date of death. The primary hypothesis will test whether OS is increased in patients treated with irinotecan liposome injection

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:40 months
Safety Issue:
Description:Progression-free survival is the time from randomization to the first documented objective disease progression (PD) using RECIST v1.1 or death due to any cause, whichever occurs first
Measure:Objective Response
Time Frame:40 months
Safety Issue:
Description:Objective response is defined as the time from randomization to date of progression or death. Objective response rate (ORR) is the proportion of patients who achieve partial response or complete response according to RECIST v1.1 guidelines
Measure:Proportion of Patients with Symptom Improvement
Time Frame:Randomization to 30 Days after permanent treatment termination
Safety Issue:
Description:Patient-reported EORTC-QLQ symptom scales for cough, dyspnea, and fatigue
Measure:Incidence of treatment-emergent adverse events, serious adverse events and laboratory abnormalities
Time Frame:Enrollment to 30 days after permanent treatment termination
Safety Issue:
Description:Safety analyses (adverse events and laboratory analyses) will be performed using the safety population, defined as all patients receiving any study drug.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ipsen

Last Updated

October 23, 2020