Phase 2 Study of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC)
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Alisertib; Placebo; Paclitaxel
Intervention description: Alisertib tablets; Placebo matching tablets; Paclitaxel intravenous injection
Intervention MeSH terms: Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 178.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      This is a two-arm, randomized, double-blind, placebo-controlled, multicenter, phase 2 study
      designed to is to determine if the combination treatment can improve progression free
      survival (defined as the time from the date of randomization to the date of first
      documentation of disease progression or death, whichever occurs first) when compared with
      placebo + paclitaxel.
    

Eligibility criteria:

        Inclusion Criteria

        Each participant must meet all the following inclusion criteria to be enrolled in the
        study:

          1. Male or female participants ≥ 18 years old.

          2. Have a pathologically (histology or cytology) confirmed diagnosis of SCLC.

          3. Have received and progressed after a platinum-based standard chemotherapy regimen for
             first line treatment of SCLC, either limited stage (LS) or extensive stage (ES).

          4. Have measurable disease within ≤ 2 weeks before randomization. Clear radiographic
             evidence of disease progression after initial therapy should have been documented.

          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0-1).

          6. Participants with treated brain metastases (surgery, whole or stereotactic brain
             radiation) are allowed provided the lesions have been stable for at least 2 weeks and
             the participant is off steroids or is on a stable dose of steroids. Participants
             should be without neurologic dysfunction that would confound the evaluation of
             neurological and/or other AEs.

        Exclusion Criteria

        Participants meeting any of the following exclusion criteria are not to be randomized to
        treatment:

          1. Any prior therapy for second-line treatment of SCLC.

          2. Participants who relapsed ≥ 180 days after their response to first-line treatment.

          3. Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent,
             including alisertib, or any other investigational agent.

          4. Prior treatment with paclitaxel or any other taxane agent.

          5. Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.

          6. Any comorbid condition or unresolved toxicity that would preclude administration of
             alisertib or weekly paclitaxel.

          7. Prior history of ≥ Grade 2 neurotoxicity that is not resolved to ≤ Grade 1.

          8. Participants with symptomatic and/or progressive brain metastases or with
             carcinomatous meningitis.

          9. Treatment with clinically significant enzyme inducers within 14 days prior to the
             first dose of alisertib and during study conduct. Major prohibited enzyme inducers
             include: phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine,
             and St. John's wort.

         10. Inability to swallow alisertib or other orally administered medications.

         11. Requirement for administration of proton pump inhibitor (PPI), H2 antagonist, or
             pancreatic enzymes.

         12. Diagnosed with or treated for another malignancy within 2 years before the first dose
             of study drug, or previously diagnosed with another malignancy and have any evidence
             of residual disease.

         13. Other severe acute or chronic medical or psychiatric condition(s) per protocol.

         14. History of myocardial infarction, unstable symptomatic ischemic heart disease,
             uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac
             arrhythmias of Grade > 2, thromboembolic events (eg, deep vein thrombosis, pulmonary
             embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg,
             pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving
             the first dose of study drug.

         15. Known history of human immunodeficiency virus (HIV) infection, hepatitis B or
             hepatitis C.

         16. Surgery within 3 weeks (or 2 weeks for a minor surgery) before study enrollment and
             not fully recovered to baseline or to a stable clinical status.

         17. Participants who are pregnant, lactating, or do not agree to use effective methods of
             contraception during the study treatment period through 6 months after the last dose
             of study drug per protocol.