This trial is active, not recruiting.

Condition small cell lung cancer (sclc)
Treatments alisertib (mln8237), placebo, paclitaxel 60 mg/m2, paclitaxel 80 mg/m2
Phase phase 2
Target ARK-1
Sponsor Millennium Pharmaceuticals, Inc.
Start date February 2014
End date March 2016
Trial size 178 participants
Trial identifier NCT02038647, 2013-003713-18, C14018, DRKS00007849, U1111-1154-9805


This is a two-arm, randomized, double-blind, placebo-controlled, multicenter, phase 2 study designed to evaluate the efficacy and safety of alisertib, an Aurora A kinase inhibitor, in combination with paclitaxel compared with placebo + paclitaxel in patients with SCLC who have relapsed or did not respond to first line standard therapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
alisertib (mln8237)
40 mg orally twice a day - 3 days on/4 days off weekly for 3 weeks in a 28-day cycle.
paclitaxel 60 mg/m2
60 mg/m2 intravenously (IV) once a week for 3 weeks in a 28-day cycle.
(Placebo Comparator)
0 mg orally twice a day - 3 days on/4 days off for 3 weeks in a 28-day cycle.
paclitaxel 80 mg/m2
80 mg/m2 intravenously (IV) once a week for 3 weeks in a 28-day cycle.

Primary Outcomes

Progression-free survival (PFS)
time frame: Up to 22 months

Secondary Outcomes

Overall survival (OS)
time frame: Up to 22 months
Overall response rate (ORR), including complete response rate (CRR)
time frame: Duration of study until disease progression up to 22 months.
Safety and health related quality of life (HRQOL)
time frame: From screening period to the specified number of PFS events up to 22 months.
Biomarker correlative studies including circulating tumor cells and circulating DNA assessments
time frame: Twice in cycle 1 in a 28-day cycle
Disease control rate (DCR)
time frame: From screening period to 30 days after last dose of study drug up to 22 months.
Duration of response (DOR)
time frame: From screening period to 30 days after last dose of study drug up to 22 months.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria Each patient must meet all the following inclusion criteria to be enrolled in the study: 1. Male or female patients ≥ 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. Patients 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 patient is off steroids or is on a stable dose of steroids. Patients should be without neurologic dysfunction that would confound the evaluation of neurological and/or other AEs. Exclusion Criteria Patients 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. Patients 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. Patients 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. Patients 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.

Additional Information

Official title A Randomized, Double-blind, Placebo-controlled, Phase 2 Clinical Trial of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC).
Description Randomization will be stratified by the type of relapse after primary treatment (sensitive or resistant/refractory disease) and presence of brain metastases.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Millennium Pharmaceuticals, Inc..
Location data was received from the National Cancer Institute and was last updated in April 2016.