LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib

NCT ID: NCT01828112

Last Updated: 2025-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 231 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-28
• Study Completion Date: 2023-11-10

Brief Summary

The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

Detailed Description

A total of 231 patients were randomized to one of the two treatment arms in a 1:1 ratio. Randomization was stratified by World Health Organization (WHO) performance status (0 versus 1-2) and whether the patient had brain metastases at screening. The study was planned to be ended once the final overall survival (OS) analysis was performed (at the earliest of approximately 196 deaths observed or statistical significance reached at earlier OS interim analysis).

Following an agreement between Novartis and European Medicines Agency (EMA) in May 2023 to terminate the trial earlier, this study was completed when the total number of deaths was 190. Patients who had Response Evaluation Criteria In Solid Tumors (RECIST)-defined disease progression as confirmed by the Blinded Independent Review Committee (BIRC), but who, in the opinion of the Investigator, had continued clinical benefit from study treatment on either the chemotherapy arm or the ceritinib arm, continued to receive treatment. These patients continued assessments in the treatment phase. In addition, only patients randomized to the chemotherapy arm were allowed to crossover to receive ceritinib therapy (extension treatment [ET] phase) after BIRC-confirmed, RECIST-defined disease progression, and provided they met the eligibility requirements.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ceritinib

Ceritinib 750 mg

Group Type: EXPERIMENTAL

Ceritinib

Intervention Type: DRUG

Ceritinib was the investigational treatment and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.

Chemotherapy

Chemotherapy as determined by BIRC

Group Type: ACTIVE_COMPARATOR

Pemetrexed

Intervention Type: DRUG

Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m\^2 every 21 days.

Docetaxel

Intervention Type: DRUG

Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m\^2 every 21 days.

Interventions

Ceritinib

Ceritinib was the investigational treatment and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.

Intervention Type: DRUG

Pemetrexed

Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m\^2 every 21 days.

Intervention Type: DRUG

Docetaxel

Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m\^2 every 21 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by the FDA approved Abbott FISH Test.

2. Patient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.

3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation

4. Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.

Exclusion Criteria

1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)

2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.

3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

Memorial Cancer Institute

Hollywood, Florida, United States

Cancer Specialists of North Florida

Jacksonville, Florida, United States

University Of Miami

Miami, Florida, United States

Loyola University Medical Center

Marywood, Illinois, United States

Uni Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Texas Oncology-Sugarland

Sugar Land, Texas, United States

Texas Oncology Cancer Care and Research Center

Waco, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Swedish Cancer Institute

Seattle, Washington, United States

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Edegem, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Marseille, Bouches Du Rhone, France

Novartis Investigative Site

Besançon, , France

Novartis Investigative Site

Brest, , France

Novartis Investigative Site

Caen, , France

Novartis Investigative Site

Le Mans, , France

Novartis Investigative Site

Mulhouse, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Strasbourg, , France

Novartis Investigative Site

Suresnes, , France

Novartis Investigative Site

Bad Berka, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Esslingen am Neckar, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Tübingen, , Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Pokfulam, , Hong Kong

Novartis Investigative Site

Limerick, Co Limerick, Ireland

Novartis Investigative Site

Dublin, , Ireland

Novartis Investigative Site

Kfar Saba, , Israel

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Avellino, AV, Italy

Novartis Investigative Site

Monza, MB, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Perugia, PG, Italy

Novartis Investigative Site

Pisa, PI, Italy

Novartis Investigative Site

Aviano, PN, Italy

Novartis Investigative Site

Reggio Emilia, RE, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Orbassano, TO, Italy

Novartis Investigative Site

Verona, VR, Italy

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Kashiwa, Chiba, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Akashi, Hyōgo, Japan

Novartis Investigative Site

Okayama, Okayama-ken, Japan

Novartis Investigative Site

Hirakata, Osaka, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Ōsaka-sayama, Osaka, Japan

Novartis Investigative Site

Takatsuki, Osaka, Japan

Novartis Investigative Site

Koto Ku, Tokyo, Japan

Novartis Investigative Site

Niigata, , Japan

Novartis Investigative Site

El Achrafiyé, , Lebanon

Novartis Investigative Site

Groningen, , Netherlands

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow Region Istra Village, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, Seocho Gu, South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

A Coruña, Galicia, Spain

Novartis Investigative Site

Santiago de Compostela, Galicia, Spain

Novartis Investigative Site

Valencia, Valencia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Lucerne, , Switzerland

Novartis Investigative Site

Sankt Gallen, , Switzerland

Novartis Investigative Site

Pendik Istanbul, Turkey, Turkey (Türkiye)

Novartis Investigative Site

Istanbul, TUR, Turkey (Türkiye)

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Cheltenham, Gloucestershire, United Kingdom

Novartis Investigative Site

Aberdeen, Grampian Region, United Kingdom

Novartis Investigative Site

Leicester, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Southampton, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Hong Kong; Ireland; Israel; Italy; Japan; Lebanon; Netherlands; Portugal; Russia; Singapore; South Korea; Spain; Switzerland; Turkey (Türkiye); United Kingdom

References

Kiura K, Imamura F, Kagamu H, Matsumoto S, Hida T, Nakagawa K, Satouchi M, Okamoto I, Takenoyama M, Fujisaka Y, Kurata T, Ito M, Tokushige K, Hatano B, Nishio M. Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset. Jpn J Clin Oncol. 2018 Apr 1;48(4):367-375. doi: 10.1093/jjco/hyy016.

Reference Type: DERIVED

PMID: 29474558 (View on PubMed)

Shaw AT, Kim TM, Crino L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. doi: 10.1016/S1470-2045(17)30339-X. Epub 2017 Jun 9.

Reference Type: DERIVED

PMID: 28602779 (View on PubMed)

Other Identifiers

2012-005637-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLDK378A2303

Identifier Type: -

Identifier Source: org_study_id