Small Cell Lung CancerPhase 2NCT02038647
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)
A Phase 2 study testing Alisertib and Paclitaxel in people with Small Cell Lung Cancer, run by Millennium Pharmaceuticals, Inc. at 61 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- Alisertib and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 178 participants
- Where
- 61 sitesin 10 countries
- Study dates
- 12 May 2014to 10 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each participant must meet all the following inclusion criteria to be enrolled in the study:
- Male or female participants ≥ 18 years old.
- Have a pathologically (histology or cytology) confirmed diagnosis of SCLC.
- 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).
- Have measurable disease within ≤ 2 weeks before randomization. Clear radiographic evidence of disease progression after initial therapy should have been documented.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0-1).
- 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.
Who cannot join
- Participants meeting any of the following exclusion criteria are not to be randomized to treatment:
- Any prior therapy for second-line treatment of SCLC.
- Participants who relapsed ≥ 180 days after their response to first-line treatment.
- Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib, or any other investigational agent.
- Prior treatment with paclitaxel or any other taxane agent.
- Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.
Show all 18Show fewer
- Any comorbid condition or unresolved toxicity that would preclude administration of alisertib or weekly paclitaxel.
- Prior history of ≥ Grade 2 neurotoxicity that is not resolved to ≤ Grade 1.
- Participants with symptomatic and/or progressive brain metastases or with carcinomatous meningitis.
- 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.
- Inability to swallow alisertib or other orally administered medications.
- Requirement for administration of proton pump inhibitor (PPI), H2 antagonist, or pancreatic enzymes.
- 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.
- Other severe acute or chronic medical or psychiatric condition(s) per protocol.
- 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.
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C.
- 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.
- 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.
Trial locations and contacts
61 sites in 10 countries.
61 sites in 10 countries
United States21 sites
Study site
Ann Arbor, Michigan
Study site
Atlanta, Georgia
Study site
Boca Raton, Florida
Study site
Boston, Massachusetts
Study site
Chicago, Illinois
Study site
Cleveland, Ohio
Study site
Detroit, Michigan
Study site
Hershey, Pennsylvania
Study site
Hollywood, Florida
Study site
Houston, Texas
Study site
Los Angeles, California
Study site
Minneapolis, Minnesota
Study site
Nashville, Tennessee
Study site
New Haven, Connecticut
Study site
Orlando, Florida
Study site
Philadelphia, Pennsylvania
Study site
Pittsburgh, Pennsylvania
Study site
Sacramento, California
Study site
Seattle, Washington
Study site
Tampa, Florida
Study site
Washington D.C., District of Columbia
Belgium6 sites
Study site
Edegem
Study site
Ghent
Study site
Kortrijk
Study site
Leuven
Study site
Mons
Study site
Roeselare
France6 sites
Study site
Grenoble
Study site
Lyon
Study site
Marseille
Study site
Paris
Study site
Pessac
Study site
Rennes
Hungary5 sites
Study site
Budapest
Study site
Farkasgyepű
Study site
Szolnok
Study site
Tatabánya
Study site
Törökbálint
Spain5 sites
Study site
A Coruña
Study site
Barcelona
Study site
Girona
Study site
Madrid
Study site
Seville
Czechia4 sites
Study site
Olomouc
Study site
Ostrava
Study site
Prague
Study site
Ústí nad Labem
Germany4 sites
Study site
Berlin
Study site
Frankfurt
Study site
Freiburg im Breisgau
Study site
Lübeck
Poland4 sites
Study site
Gdansk
Study site
Mrozy
Study site
Warsaw
Study site
Wodzisław Śląski
Canada3 sites
Study site
Edmonton, Alberta
Study site
Greenfield Park
Study site
Hamilton, Ontario
About this study
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).
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.
Read the detailed 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 were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there is an urgent medical need) and participants were stratified at baseline as to whether brain mets were present or not; whether they were sensitive to prior therapy or were relapsed/refractory to prior therapy; and by world region:
- 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 was approximately up to 22 months. Participants made multiple visits to the clinic, and were 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.
- Conditions
- Small Cell Lung Cancer
- Being tested
- Alisertib, Placebo, Paclitaxel
- Keywords
- Drug therapy
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlisertibDrug
Also called MLN8237
Alisertib tablets
PlaceboDrug
Placebo matching tablets
PaclitaxelDrug
Paclitaxel intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| Alisertib (MLN8237) + Paclitaxel | Experimental | 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 until disease progression (Up to 17 Cycles). Receives: Drug: Alisertib; Drug: Paclitaxel |
| Placebo + Paclitaxel | 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 until disease progression (Up to 22 Cycles). Receives: Drug: Placebo; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines
PFS is defined as time in days from start of study treatment to first documentation of objective tumor progression based on Investigator's assessment or up to death due to any cause, whichever occurs first based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Progressive disease (PD) was defined as ≥20% increase in sum longest diameter (LD) in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)
Secondary outcomes (12)
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with treatment. An AE can be any unfavorable and unintended sign (eg, clinically significant abnormal laboratory finding), symptom, or disease temporally associated with use of drug, whether or not it is considered related to drug. A treatment-emergent adverse event (TEAE) is defined as an AE with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) is any experience that suggests significant hazard, contraindication, side effect or precaution that:results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is congenital anomaly/birth defect or is medically significant per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Measured: From the first dose through 30 days after the last dose of study medication: data cut-off 03 January 2016 (Up to 10.8 months)
Overall Survival (OS)
OS was defined as the time in days from the date of randomization to the date of death due to any cause.
Measured: Contact every 2 months after EOT/disease progression 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 22 months)
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieved CR or partial response (PR) as best response based on Investigator's assessment according to RECIST v 1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as ≥ 30% decrease in sum of LD of target lesions in reference to Baseline sum LD.
Measured: Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Complete Response Rate (CRR)
CRR is defined as the percentage of participants who achieved CR as best response and based on Investigator's assessment according to RECIST v 1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
Measured: Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Disease Control Rate (DCR)
DCR was defined as the percentage of participants who achieved CR, PR, or SD (when SD was a minimum of 8 weeks in duration). Duration of SD was defined as the time from the date of randomization to the date of first documentation of disease progression for participants who achieved SD as their best overall response. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as ≥ 30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders. PR was defined as ≥ 30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: From first documented response until disease progression until data cut-off 03 January 2016 (approximately 9.8 months)
Change From Baseline in Symptom (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) Score at Cycle 5
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is 30-item questionnaire with 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (fatigue, nausea, vomiting and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions use 7-point scale (1=very poor - 7=Excellent). Total Score=0-100 scale; for 5 functional scales and global quality-of-life scale, a higher score=a better level of functioning. For symptoms scale, higher score= higher level of symptoms. EORTC QLQ-LC13 is considered as standard instrument to assess the quality of life (QL) of lung cancer participants. Total Score=0-100. Higher score=increase in level of symptomatology. The change between (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) score collected at Cycle 5 relative to baseline.
Measured: Baseline up to Cycle 5 (approximately 4.6 months)
Percentage of Participants Experiencing Symptom Relief
Percentage of participants experiencing symptom relief, including coughing relief, dyspnea relief, and pain relief. Coughing relief is defined as a decrease from baseline ≥ 10 in QLQ-LC13 cough scale/item score. Dyspnea relief is defined as a decrease from baseline ≥ 10 in QLQ-C30 dyspnea scale/item score. Pain relief is defined as a decrease from baseline ≥ 10 in QLQ-C30 pain scale score. EORTC QLQ-C30 is 30-item questionnaire with 5 functional scales, 1 global health status scale, 3 symptom scales, 6 single items. Total Score=0-100 scale; for 5 functional scales and global quality-of-life scale, a higher score=a better level of functioning. For symptoms scale, higher score= higher level of symptoms. EORTC QLQ-LC13 is considered as standard instrument to assess the QL of lung cancer participants. Total Score=0-100. Higher score=increase in level of symptomatology.
Measured: Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Time to Symptom Relief
Time to symptom (coughing/dyspnea/pain) relief was defined as the time from the date of randomization to the date of first detection of coughing/dyspnea/pain relief, respectively.
Measured: Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Time to Symptom Progression
Time to coughing/dyspnea/pain progression was defined as time from the date of randomization to date of first detection of progression. Coughing progression was defined as increase from baseline ≥10 in QLQ-LC13 cough scale/item score. Dyspnea progression was defined as increase from baseline ≥10 in QLQ-C30 dyspnea scale/item score. Pain progression was defined as increase from baseline ≥10 in QLQ-C30 pain scale score. EORTC QLQ-C30 is 30-item questionnaire with 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (fatigue, nausea, vomiting and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-LC13 is 13-item scale for assessing treatment-specific symptoms in lung cancer. Total Score= 0-100 scale; for 5 functional scales and global quality-of-life scale, higher score=better level of functioning. For symptoms scale, higher score=higher level of symptoms.
Measured: Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Observed Plasma Concentration for Alisertib
Measured: Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours (hrs) post-dose
Observed Plasma Concentration for Paclitaxel
Measured: Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2014 (estimated)
- Study start12 May 2014
- Primary completion3 Jan 2016
- Study completion10 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02038647
- Sponsor's protocol ID
- C14018
- Other IDs
- 2013-003713-18, U1111-1154-9805, DRKS00007849
- Status last verified
- Nov 2018
- First submitted
- 4 Dec 2013
- Last updated
- 27 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Owonikoko TK, Niu H, Nackaerts K, Csoszi T, Ostoros G, Mark Z, Baik C, Joy AA, Chouaid C, Jaime JC, Kolek V, Majem M, Roubec J, Santos ES, Chiang AC, Speranza G, Belani CP, Chiappori A, Patel MR, Czebe K, Byers L, Bahamon B, Li C, Sheldon-Waniga E, Kong EF, Williams M, Badola S, Shin H, Bedford L, Ecsedy JA, Bryant M, Jones S, Simmons J, Leonard EJ, Ullmann CD, Spigel DR; C14018 study investigators. Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses. J Thorac Oncol. 2020 Feb;15(2):274-287. doi: 10.1016/j.jtho.2019.10.013. Epub 2019 Oct 23.
PubMed 31655296
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT02038647
- Acronym / sponsor ID
- C14018
- Conditions
- Small Cell Lung Cancer
- Keywords
- Drug therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 May 2014 (actual)
- Primary completion
- 3 Jan 2016 (actual)
- Study completion
- 10 Jul 2017 (actual)
- First posted
- 16 Jan 2014 (estimated)
- Results
- Posted 27 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there is an urgent medical need) and participants were stratified at baseline as to whether brain mets were present or not; whether they were sensitive to prior therapy or were relapsed/refractory to prior therapy; and by world region:
- 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 was approximately up to 22 months. Participants made multiple visits to the clinic, and were 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alisertib (MLN8237) + Paclitaxel | Experimental | Drug: Alisertib, Drug: PaclitaxelAlisertib 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 until disease progression (Up to 17 Cycles). |
| Placebo + Paclitaxel | Placebo comparator | Drug: Placebo, Drug: PaclitaxelAlisertib 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 until disease progression (Up to 22 Cycles). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Each participant must meet all the following inclusion criteria to be enrolled in the study:
- Male or female participants ≥ 18 years old.
- Have a pathologically (histology or cytology) confirmed diagnosis of SCLC.
- 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).
- Have measurable disease within ≤ 2 weeks before randomization. Clear radiographic evidence of disease progression after initial therapy should have been documented.
Key exclusion criteria (18 listed)
- Participants meeting any of the following exclusion criteria are not to be randomized to treatment:
- Any prior therapy for second-line treatment of SCLC.
- Participants who relapsed ≥ 180 days after their response to first-line treatment.
- Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib, or any other investigational agent.
- Prior treatment with paclitaxel or any other taxane agent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlisertibAlso: MLN8237Alisertib tablets | Drug | Alisertib (MLN8237) + Paclitaxel |
| PlaceboPlacebo matching tablets | Drug | Placebo + Paclitaxel |
| PaclitaxelPaclitaxel intravenous injection | Drug | Alisertib (MLN8237) + Paclitaxel, Placebo + Paclitaxel |
Primary outcome
Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines
Time frame: Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)
PFS is defined as time in days from start of study treatment to first documentation of objective tumor progression based on Investigator's assessment or up to death due to any cause, whichever occurs first based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Progressive disease (PD) was defined as ≥20% increase in sum longest diameter (LD) in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
12 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: data cut-off 03 January 2016 (Up to 10.8 months)
Overall Survival (OS)
Time frame: Contact every 2 months after EOT/disease progression 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 22 months)
Overall Response Rate (ORR)
Time frame: Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Complete Response Rate (CRR)
Time frame: Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Disease Control Rate (DCR)
Time frame: Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Duration of Response (DOR)
Time frame: From first documented response until disease progression until data cut-off 03 January 2016 (approximately 9.8 months)
Change From Baseline in Symptom (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) Score at Cycle 5
Time frame: Baseline up to Cycle 5 (approximately 4.6 months)
Percentage of Participants Experiencing Symptom Relief
Time frame: Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Time to Symptom Relief
Time frame: Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Time to Symptom Progression
Time frame: Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Observed Plasma Concentration for Alisertib
Time frame: Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours (hrs) post-dose
Observed Plasma Concentration for Paclitaxel
Time frame: Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31655296Owonikoko TK, Niu H, Nackaerts K, Csoszi T, Ostoros G, Mark Z, Baik C, Joy AA, Chouaid C, Jaime JC, Kolek V, Majem M, Roubec J, Santos ES, Chiang AC, Speranza G, Belani CP, Chiappori A, Patel MR, Czebe K, Byers L, Bahamon B, Li C, Sheldon-Waniga E, Kong EF, Williams M, Badola S, Shin H, Bedford L, Ecsedy JA, Bryant M, Jones S, Simmons J, Leonard EJ, Ullmann CD, Spigel DR; C14018 study investigators. Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses. J Thorac Oncol. 2020 Feb;15(2):274-287. doi: 10.1016/j.jtho.2019.10.013. Epub 2019 Oct 23.
Related trials for Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Millennium Pharmaceuticals, Inc.
61 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alisertib and Paclitaxel in people with Small Cell Lung Cancer, run by Millennium Pharmaceuticals, Inc. at 61 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in United States, Belgium, France, Hungary, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines (time frame: Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02038647, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2018.