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)

NCT02038647 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: C140182013-003713-18U1111-1154-9805DRKS00007849
• Study Type: interventional
• Target: 178
• Locations: 10 countries
• Sites: 61

Brief 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.

Conditions

Small Cell Lung Cancer

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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)

  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)

  Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)

• Complete Response Rate (CRR)

  Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)

• Disease Control Rate (DCR)

  Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)

Other Outcomes (2)

• Biomarker Correlative Studies Including Circulating Tumor Cells and Circulating DNA Assessments

  Day 1 cycle 1 in a 28-day cycle

• Health Related Quality of Life (HRQOL )

  Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)

Study Arms (2)

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).

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).

Drug: Placebo; Drug: Paclitaxel

Interventions

Alisertib DRUG

Alisertib tablets

Also known as: MLN8237

Alisertib (MLN8237) + Paclitaxel

Placebo DRUG

Placebo matching tablets

Placebo + Paclitaxel

Paclitaxel DRUG

Paclitaxel intravenous injection

Alisertib (MLN8237) + Paclitaxel; Placebo + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (61)

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Los Angeles, California, United States

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Sacramento, California, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Boca Raton, Florida, United States

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Hollywood, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Cleveland, Ohio, United States

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Hershey, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Edegem, Belgium

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Ghent, Belgium

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Kortrijk, Belgium

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Leuven, Belgium

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Mons, Belgium

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Roeselare, Belgium

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Edmonton, Alberta, Canada

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Hamilton, Ontario, Canada

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Greenfield Park, Canada

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Olomouc, Czechia

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Ostrava, Czechia

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Prague, Czechia

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Ústí nad Labem, Czechia

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Grenoble, France

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Lyon, France

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Marseille, France

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Paris, France

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Pessac, France

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Rennes, France

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Berlin, Germany

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Frankfurt, Germany

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Freiburg im Breisgau, Germany

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Lübeck, Germany

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Budapest, Hungary

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Farkasgyepű, Hungary

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Szolnok, Hungary

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Tatabánya, Hungary

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Törökbálint, Hungary

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Milan, Italy

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Orbassano, Italy

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Parma, Italy

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Gdansk, Poland

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Mrozy, Poland

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Warsaw, Poland

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Wodzisław Śląski, Poland

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A Coruña, Spain

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Barcelona, Spain

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Girona, Spain

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Madrid, Spain

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Seville, Spain

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Related Publications (1)

• 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.

  PMID: 31655296 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

MLN 8237; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2013
• First Posted: January 16, 2014
• Study Start: May 12, 2014
• Primary Completion: January 3, 2016
• Study Completion: July 10, 2017
• Last Updated: December 27, 2018
• Results First Posted: December 27, 2018

Record last verified: 2018-11

Locations

US (21); FR (6); DE (4); HU (5); IT (3); BE (6); PL (4); ES (5); CZ (4); CA (3)