Study of Irinotecan Liposome Injection (ONIVYDE®) in Patients With Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Irinotecan liposome injection; Topotecan
Intervention description: IV; IV
Intervention MeSH terms: Irinotecan; Topotecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: Open Label
Enrollment: 491.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

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.