E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041067 |
E.1.2 | Term | Small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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, pulmonary fibrosis, active uncontrolled bleeding, or a known bleeding
diathesis) less than 6 months before inclusion
11. New York Heart Association Class III or IV congestive heart failure, ventricular
arrhythmias or uncontrolled blood pressure
12. Active infection (e.g. acute bacterial infection, tuberculosis, active hepatitis B/C or active human immunodeficiency virus) which in the investigator’s opinion
might compromise the patient’s participation in the trial or affect the study
outcome
13. Known hypersensitivity to any of the components of irinotecan liposome
injection, other liposomal products, or topotecan
14. Clinically significant gastrointestinal disorder including hepatic disorders,
bleeding, inflammation, occlusion, or diarrhea > grade 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy end point is Overall Survival |
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E.5.1.1 | 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. |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the final overall survival analyis |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
France |
Germany |
Spain |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |