Small cell lung cancer MedDRA version: 20.0 Level: PT Classification code 10041067 Term: Small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Onivyde
Product Name: irinotecan liposome
Product Code: MM-398
Pharmaceutical Form: Injection
INN or Proposed INN: IRINOTECAN
CAS Number: 97682-44-5
Current Sponsor code: MM-398
Other desc
Sponsors
Ipsen Bioscience, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria 1. At least 18 years of age 2. Able to understand and provide the study informed consent 3. ECOG performance status of 0 or 1 4. Life expectancy =12 weeks Disease Specific Inclusion Criteria 5. Histopathologically or cytologically confirmed small cell lung cancer according to the International Association for the Study of Lung Cancer (IASLC) histopathological classification. Mixed or combined subtypes according to the IASLC are not allowed. 6. Evaluable disease as defined by RECIST Version 1.1 guidelines (patients with non-target lesions only are eligible) 7. Radiologically confirmed progression on or after first-line platinum based chemotherapy (carboplatin or cisplatin) or chemo-radiation including platinumbased chemotherapy for treatment of limited or extensive stage small cell lung cancer 8. 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) Hematologic, Biochemical and Organ Function Inclusion Criteria 9. During the Screening period, adequate bone marrow reserves as evidenced by: a. Absolute neutrophil count > 1,500 cells/µL (1.5 x 109/L) without the use of hematopoietic growth factors within the immediately preceding 14 days; and b. Platelet count > 100,000 cells/µL (100 x 109/L); and c. Hemoglobin > 9 g/dL; transfusions are allowed 10. Adequate hepatic function as evidenced by: a. Serum total bilirubin within normal range for the institution b. Aspartate aminotransferase and alanine aminotransferase = 2.5 x upper limit of normal (ULN) (= 5 x ULN is acceptable if liver metastasis is present) c. Serum albumin =3.0 g/dL (=30 g/L) 11. Adequate renal function as evidenced by a serum creatinine = 1.5 x ULN and creatinine clearance =40 mL/min. Actual body weight should be used for calculating creatinine clearance using the Cockcroft-Gault Equation (except for patients with body mass index > 30 kg/m2 when lean body weight should be used instead): Serum Creatinine (mg/min)= (140-Age (years)×(Weight(kg)) ×Sex 72× Serum Creatinine (mg/dL) ? ? ? ? where Sex 1 for males and 0.85 for females. ? 12. Electrocardiogram during the Screening period without any clinically significant findings, per the investigator’s assessment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 286 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: General Exclusion Criteria 1. 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 2. Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test. Both male and female patients of reproductive potential must agree to use a highly effective method of birth control, during the study and for 4 months following the last dose of study drug. Disease Specific Exclusion Criteria 3. Patients with large cell neuroendocrine carcinoma 4. Patients who received any of the following treatments: a. Prior treatment regimens with irinotecan, topotecan or any other topoisomerase I inhibitor including investigational topoisomerase I inhibitors. b. Retreatment of the same platinum-based after relapse. c. Any antibody-drug conjugates or molecular targeted agents (e.g. poly ADP-ribose polymerase inhibitors), either alone or in combination with other treatments. d. More than one line of immunotherapy (e.g. nivolumab, pembrolizumab, ipilimumab, atezolizumab, tremelimumab and/or durvalumab). One line of immunotherapy is allowed, which is defined as the following: monotherapy or combination of immunotherapy agents given as either (i) in combination with chemotherapy followed by immunotherapy maintenance in the first line setting, (ii) only as a maintenance following response to first-line chemotherapy or (iii) immunotherapy given as second line treatment following progression. e. Any other additional regimen of prior cytotoxic chemotherapy, not described above. 5. Patients with a history of immunotherapy induced colitis or pneumonitis, based on clinical assessment and/or confirmed by biopsy 6. Patients with the following CNS metastasis: a. Patients who developed new or progressive brain metastasis following prophylactic and/or therapeutic cranial radiation (whole brain or stereotactic radiation) b. Patients with symptomatic CNS metastasis (a patient with brain metastasis who received cranial radiotherapy is eligible if asymptomatic for neurological symptoms for =2 weeks after cranial radiotherapy and is off corticosteroids for treatment of CNS metastasis). Patients with asymptomatic brain metastasis are eligible to be enrolled directly to the study c. Patients with carcinomatous meningitis 7. 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 8. Have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis [carcinoma in situ]) or any previous cancer curatively treated >3 years ago without evidence of recurrence. 9. 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 Hematologic, Biochemical and Organ Function Exclusion Criteria 10. Severe cardiovascular and pulmonary disease (e.g. myocardial infarction, unstable angina pectoris, coronary angioplasty or stenting, deep vein thrombosis, stroke,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective Part I -Describe the safety and tolerability of irinotecan liposome injection monotherapy administered every 2 weeks - To determine the irinotecan liposome injection monotherapy dose (85 mg/m2 or 70 mg/m2 administered every 2 weeks) for Part 2 of this study Primary Objective Part II To compare overall survival following treatment with irinotecan liposome injection with overall survival following treatment with IV topotecan.;Secondary Objective: secondary Objective Part I: To assess the preliminary efficacy of irinotecan liposome injection (at either the 85 mg/m2 dose level or the 70 mg/m2 dose level as determined by: Objective response rate (ORR) Progression free survival (PFS) Overall survival (OS) Secondary Objective Part II To compare the following between the treatment arms: ? Progression free survival (PFS) ? Objective response Rate (ORR) ? Proportion of patients with improvement in symptoms as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) ? Safety profile;Primary end point(s): Primary Efficacy end point is Overall Survival;Timepoint(s) of evaluation of this end point: Overall survival is defined as the number of months from the date of the first dose of study drug in Part 2 to the date of death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy end points are Progression free survival, objective response rate and proportion of patients with improvement in patient-reported outcomes.;Timepoint(s) of evaluation of this end point: At the final overall survival analyis | — |
Countries
Australia, Austria, Belgium, France, Germany, Hungary, Italy, Romania, Spain, Taiwan, United States
Contacts
Public ContactGlobal Drug Development
Ipsen Bioscience, Inc
Outcome results
None listed