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

NCT01828112 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CLDK378A23032012-005637-36
• Study Type: interventional
• Target: 231
• Locations: 20 countries
• Sites: 97

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; ALK; LDK378; Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; lung cancer; lung adenocarcinoma; Non small cell lung carcinoma; Non small cell lung cancer; NSCLC; chemotherapy; ALK-positive; ALK-rearranged advanced non-small cell lung cancer; crizotinib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC)

  PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

  From the date of randomization to the date of first radiologically documented disease progression or death due to any cause up to approximately 24 months

Secondary Outcomes (25)

• Overall Survival (OS)

  Up to approximately 114 months

• Progression Free Survival (PFS) Per Investigator Assessment

  Up to approximately 84 months

• Overall Response Rate (ORR) Per BIRC

  Up to approximately 54 months

• Overall Response Rate (ORR) Per Investigator Assessment

  Up to approximately 93 months

• Duration of Response (DOR) Per BIRC

  Up to approximately 54 months

Study Arms (2)

Ceritinib

EXPERIMENTAL

Ceritinib 750 mg

Drug: Ceritinib

Chemotherapy

ACTIVE COMPARATOR

Chemotherapy as determined by BIRC

Drug: Pemetrexed; Drug: Docetaxel

Interventions

Ceritinib 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.

Ceritinib

Pemetrexed 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.

Chemotherapy

Docetaxel 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.

Chemotherapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
• Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (97)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

University Of Miami

Miami, Florida, 33136, United States

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Loyola University Medical Center

Marywood, Illinois, 60153, United States

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Uni Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

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Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma, 74136, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Sugarland

Sugar Land, Texas, 77479, United States

Location

Texas Oncology Cancer Care and Research Center

Waco, Texas, 76712, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

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Novartis Investigative Site

Edegem, 2650, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

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Novartis Investigative Site

Marseille, Bouches Du Rhone, 13915, France

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Novartis Investigative Site

Besançon, 25030, France

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Novartis Investigative Site

Brest, 29609, France

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Novartis Investigative Site

Caen, 14021, France

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Novartis Investigative Site

Le Mans, 72000, France

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Novartis Investigative Site

Mulhouse, 68070, France

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Novartis Investigative Site

Paris, 75970, France

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Novartis Investigative Site

Strasbourg, F 67085, France

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Novartis Investigative Site

Suresnes, 92150, France

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Novartis Investigative Site

Bad Berka, 99438, Germany

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Novartis Investigative Site

Cologne, 51109, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Esslingen am Neckar, 73730, Germany

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Novartis Investigative Site

Frankfurt, 60590, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Ulm, 89081, Germany

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Novartis Investigative Site

Hong Kong, Hong Kong

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Pokfulam, Hong Kong

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Limerick, Co Limerick, V94 YX29, Ireland

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Dublin, DO4, Ireland

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Novartis Investigative Site

Kfar Saba, 44281, Israel

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Novartis Investigative Site

Ramat Gan, 52621, Israel

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Avellino, AV, 83100, Italy

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Monza, MB, 20900, Italy

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Novartis Investigative Site

Milan, MI, 20132, Italy

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Perugia, PG, 06129, Italy

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Pisa, PI, 56124, Italy

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Novartis Investigative Site

Aviano, PN, 33081, Italy

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Reggio Emilia, RE, 42123, Italy

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Roma, RM, 00189, Italy

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Orbassano, TO, 10043, Italy

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Novartis Investigative Site

Verona, VR, 37126, Italy

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Novartis Investigative Site

Nagoya, Aichi-ken, 464 8681, Japan

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Kashiwa, Chiba, 277 8577, Japan

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Fukuoka, Fukuoka, 811-1395, Japan

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Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

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Novartis Investigative Site

Akashi, Hyōgo, 673-8558, Japan

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Novartis Investigative Site

Okayama, Okayama-ken, 700-8558, Japan

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Novartis Investigative Site

Hirakata, Osaka, 573-1191, Japan

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Novartis Investigative Site

Osaka, Osaka, 541-8567, Japan

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Novartis Investigative Site

Ōsaka-sayama, Osaka, 589 8511, Japan

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Novartis Investigative Site

Takatsuki, Osaka, 569-8686, Japan

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Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

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Novartis Investigative Site

Niigata, 951 8520, Japan

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Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

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Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

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Novartis Investigative Site

Lisbon, 1649 035, Portugal

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Novartis Investigative Site

Moscow, 115478, Russia

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Novartis Investigative Site

Moscow Region Istra Village, 143423, Russia

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Novartis Investigative Site

Saint Petersburg, 197022, Russia

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Novartis Investigative Site

Singapore, 119074, Singapore

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Novartis Investigative Site

Singapore, 168583, Singapore

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Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Seoul, 03722, South Korea

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Novartis Investigative Site

Seoul, 05505, South Korea

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Novartis Investigative Site

Seoul, 06351, South Korea

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Novartis Investigative Site

Seville, Andalusia, 41009, Spain

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Novartis Investigative Site

Seville, Andalusia, 41013, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08028, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

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Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

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Novartis Investigative Site

Valencia, Valencia, 46010, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Novartis Investigative Site

Madrid, 28222, Spain

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Novartis Investigative Site

Lucerne, 6000, Switzerland

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Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

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Novartis Investigative Site

Pendik Istanbul, Turkey, 34899, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06230, Turkey (Türkiye)

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Novartis Investigative Site

Cheltenham, Gloucestershire, GL53 7AN, United Kingdom

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Novartis Investigative Site

Aberdeen, Grampian Region, AB25 2ZN, United Kingdom

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Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

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Novartis Investigative Site

London, SE1 9RT, United Kingdom

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Novartis Investigative Site

Southampton, SO30 3JB, United Kingdom

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Related Publications (2)

• 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.

  PMID: 29474558 DERIVED

• 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.

  PMID: 28602779 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

ceritinib; Pemetrexed; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Although 116 patients were randomized to the Chemotherapy arm, 3 did not receive study drug and were excluded from the Safety set.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2013
• First Posted: April 10, 2013
• Study Start: June 28, 2013
• Primary Completion: January 26, 2016
• Study Completion: November 10, 2023
• Last Updated: February 7, 2025
• Results First Posted: July 27, 2017

Record last verified: 2025-01

Locations

CH (2); NL (1); PT (1); IL (2); BE (4); US (13); JP (12); ES (11); GB (5); IT (10); LE (1); KR (5); IE (2); RU (3); HK (2); CA (1); TU (3); FR (9); SG (2); DE (8)