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)

NCT ID: NCT02038647

Last Updated: 2018-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-12
• Study Completion Date: 2017-07-10

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.

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

Keywords

Drug therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alisertib (MLN8237) + Paclitaxel

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).

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib tablets

Paclitaxel

Intervention Type: DRUG

Paclitaxel intravenous injection

Placebo + Paclitaxel

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching tablets

Paclitaxel

Intervention Type: DRUG

Paclitaxel intravenous injection

Interventions

Alisertib

Alisertib tablets

Intervention Type: DRUG

Placebo

Placebo matching tablets

Intervention Type: DRUG

Paclitaxel

Paclitaxel intravenous injection

Intervention Type: DRUG

Other Intervention Names

MLN8237

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Los Angeles, California, United States

Sacramento, California, United States

New Haven, Connecticut, United States

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

Boca Raton, Florida, United States

Hollywood, Florida, United States

Orlando, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Detroit, Michigan, United States

Minneapolis, Minnesota, United States

Cleveland, Ohio, United States

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Nashville, Tennessee, United States

Houston, Texas, United States

Seattle, Washington, United States

Edegem, , Belgium

Ghent, , Belgium

Kortrijk, , Belgium

Leuven, , Belgium

Mons, , Belgium

Roeselare, , Belgium

Edmonton, Alberta, Canada

Hamilton, Ontario, Canada

Greenfield Park, , Canada

Olomouc, , Czechia

Ostrava, , Czechia

Prague, , Czechia

Ústí nad Labem, , Czechia

Grenoble, , France

Lyon, , France

Marseille, , France

Paris, , France

Pessac, , France

Rennes, , France

Berlin, , Germany

Frankfurt, , Germany

Freiburg im Breisgau, , Germany

Lübeck, , Germany

Budapest, , Hungary

Farkasgyepű, , Hungary

Szolnok, , Hungary

Tatabánya, , Hungary

Törökbálint, , Hungary

Milan, , Italy

Orbassano, , Italy

Parma, , Italy

Gdansk, , Poland

Mrozy, , Poland

Warsaw, , Poland

Wodzisław Śląski, , Poland

A Coruña, , Spain

Barcelona, , Spain

Girona, , Spain

Madrid, , Spain

Seville, , Spain

Countries

United States; Belgium; Canada; Czechia; France; Germany; Hungary; Italy; Poland; Spain

References

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.

Reference Type: DERIVED

PMID: 31655296 (View on PubMed)

Other Identifiers

2013-003713-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1154-9805

Identifier Type: REGISTRY

Identifier Source: secondary_id

DRKS00007849

Identifier Type: REGISTRY

Identifier Source: secondary_id

C14018

Identifier Type: -

Identifier Source: org_study_id