This trial is active, not recruiting.

Condition small cell lung cancer (sclc)
Treatments alisertib, placebo, paclitaxel
Phase phase 2
Target ARK-1
Sponsor Millennium Pharmaceuticals, Inc.
Start date February 2014
End date August 2017
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 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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model single group assignment
Primary purpose treatment
Masking participant, care provider, investigator, outcomes assessor
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle up to 11 cycles.
alisertib MLN8237
Alisertib tablets
Paclitaxel tablets
(Placebo Comparator)
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle up to 11 cycles.
Placebo matching tablets
Paclitaxel tablets

Primary Outcomes

Progression-Free survival (PFS)
time frame: Baseline up to Cycle 11 (28-day cycles) up to end of treatment (EOT), and then every month for 6 months and then every 2 months until disease progression, death or up to data cut-off: 03 January 2016 (approximately 11.2 months)

Secondary Outcomes

Percentage of Participants who Experience at least one Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From the first dose through 30 days after the last dose of study medication (Up to 11.2 months)
Overall survival (OS)
time frame: Every 2 months after EOT until the sooner of death, study closure, or 14 months after the last participant was randomized up to data cut-off: 3 January 2016 (approximately 11.2 months)
Overall Response Rate (ORR), Including Complete Response Rate (CRR)
time frame: Baseline up to Cycle 11 (28-day cycles) until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 11.2 months)
Disease Control Rate (DCR)
time frame: Baseline up to Cycle 11 (28-day cycles) until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 11.2 months)
Duration of response (DOR)
time frame: From first documented response until disease progression (approximately 11.2 months)
Change from Baseline in Symptom (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) Score at Each Cycle
time frame: Baseline up to Cycle 11 (10.2 months)
Percentage of Participants Experiencing Symptom Relief
time frame: Baseline up to Cycle 11 (10.2 months)
Time to Symptom Relief
time frame: Baseline up to Cycle 11 (10.2 months)
Time to Symptom Progression
time frame: Baseline up to Cycle 11 (10.2 months)
Observed Plasma Concentration for Alisertib and Paclitexel
time frame: Day 1 predose and at multiple timepoints (up to 11 hours) post-dose; Day 8, 2 hours post-dose; Day 15, 1 hour pre-dose
Health related quality of life (HRQOL )
time frame: Baseline up to Cycle 11 (up to 10.2 months)
Biomarker correlative studies including circulating tumor cells and circulating DNA assessments
time frame: Twice in cycle 1 in a 28-day cycle

Eligibility Criteria

All participants at least 18 years old.

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.

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 The drug tested in this study is called alisertib. Alisertib is being tested to treat people who have Small Cell Lung Cancer (SCLC). This study determined the safety and efficacy for alisertib when given twice a day along with paclitaxel. This open label study enrolled 178 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): - Alisertib 40 mg - Paclitaxel 60 mg/m^2 - Paclitaxel 80 mg/m^2 - Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient All participants received treatment until their disease progressed or they experienced unacceptable alisertib-related toxicity. This multi-center trial was conducted world-wide. The overall time to participate in this study is approximately up to 22 months. Participants will make multiple visits to the clinic, and will be contacted by telephone every month for 6 months after the end of treatment (EOT) for follow-up assessment of progression free survival and for overall survival every 2 months until death, study closure, or 14 months after randomization of the last participant.
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by Takeda.