LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

NCT ID: NCT01828099

Last Updated: 2025-01-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

376 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-09

Study Completion Date

2024-01-07

Brief Summary

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To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.

Detailed Description

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This was an open-label, randomized, global, Phase III study that compared the efficacy and safety of ceritinib to standard first-line chemotherapy in patients with advanced (NSCLC) harboring ALK rearrangement. The confirmation of ALK rearrangement was done using the ICH test by a Novartis designated central laboratory. Prior to the study, patients had not received any previous systemic, anti-cancer therapy, including ALK inhibitors, for newly diagnosed advanced non-squamous NSCLC.

The patients were randomized in a 1:1 ratio to either receive ceritinib (750 mg once daily, fasted) or chemotherapy. The chemotherapy regimen consisted of a platinum-based doublet with pemetrexed followed by pemetrexed maintenance in patients without progressive disease after 4 cycles.

Treatment was continued until the blinded independent review committee (BIRC) confirmed disease progression based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), occurrence of unacceptable toxicity, or meeting other discontinuation criteria. Patients in either arm were permitted to continue the assigned study treatment beyond BIRC-confirmed disease progression in case of continued clinical benefit, as determined by the Investigator.

All patients who discontinued treatment during the treatment phase for reasons other than death, lost to follow-up, pregnancy or disease progression entered the post-treatment follow-up period until disease progression, withdrawal of consent or death.

In the chemotherapy arm, patients were allowed to switch and receive ceritinib after BIRC-confirmed disease progression (extension-treatment period).

Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ceritinib

Ceritinib administered continuously through oral dosing at a dosage of 750 mg once daily in fasted state.

Group Type EXPERIMENTAL

Ceritinib

Intervention Type DRUG

Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule.

Chemotherapy

Pemetrexed plus cisplatin or carboplatin (based on Investigator's choice) for 4 cycles (Induction) followed by pemetrexed as single agent (Maintenance)

Group Type ACTIVE_COMPARATOR

Pemetrexed

Intervention Type DRUG

Pemetrexed was administered at a dose of 500 mg/m\^2 as an intravenous (iv) infusion on Day 1 of each 21-day cycle

Cisplatin

Intervention Type DRUG

Cisplatin was administered by iv infusion at a dose of 75 mg/m\^2 every 21 days for up to 4 cycles.

Carboplatin

Intervention Type DRUG

Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

Interventions

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Ceritinib

Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule.

Intervention Type DRUG

Pemetrexed

Pemetrexed was administered at a dose of 500 mg/m\^2 as an intravenous (iv) infusion on Day 1 of each 21-day cycle

Intervention Type DRUG

Cisplatin

Cisplatin was administered by iv infusion at a dose of 75 mg/m\^2 every 21 days for up to 4 cycles.

Intervention Type DRUG

Carboplatin

Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

Intervention Type DRUG

Other Intervention Names

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LDK378

Eligibility Criteria

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Inclusion Criteria

1. The patient had a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that was Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test was performed at Novartis designated central laboratories.
2. The patient had a newly diagnosed stage IIIB (who was not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with the exception of neo-adjuvant or adjuvant therapy.
3. The patient had at least one measurable lesion as defined by RECIST 1.1.

Exclusion Criteria

1. The patient had known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide, and magnesium stearate).
2. The patient had a history of severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs.
3. The patient had symptomatic central nervous system (CNS) metastases and was neurologically unstable or had 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

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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La Rioja, , Argentina

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Woolloongabba, Queensland, Australia

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Heidelberg, Victoria, Australia

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Auckland, , Australia

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Salzburg, , Austria

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Vienna, , Austria

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Fortaleza, Ceará, Brazil

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Salvador, Estado de Bahia, Brazil

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Recife, Pernambuco, Brazil

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Rio de Janiero, Rio de Janeiro, Brazil

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Natal, Rio Grande do Norte, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Itajaí, Santa Catarina, Brazil

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Barretos, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Guangzhou, Guangdong, China

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Changchun, Jilin, China

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Changchun, Jilin, China

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Shanghai, Shanghai Municipality, China

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Xi’an, Shanxi, China

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Chengdu, Sichuan, China

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Hangzhou, Zhejiang, China

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Hangzhou, Zhejiang, China

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Beijing, , China

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Beijing, , China

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Chongqing, , China

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Chongqing, , China

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Guang Dong Province, , China

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Tianjin, , China

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Bogota, Cundinamarca, Colombia

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Montería, , Colombia

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Herlev, , Denmark

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Odense C, , Denmark

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Limoges, Haute Vienne, France

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Toulon, Val De Marne, France

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Caen, , France

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Grenoble, , France

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Lille, , France

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Paris, , France

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Pierre-Bénite, , France

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Rennes, , France

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Strasbourg, , France

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Villejuif, , France

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Cologne, , Germany

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Coswig, , Germany

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Essen, , Germany

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Göttingen, , Germany

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Großhansdorf, , Germany

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Heidelberg, , Germany

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Oldenburg, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Wiesbaden, , Germany

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Athens, GR, Greece

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Heraklion Crete, , Greece

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Zalaegerszeg, Zala County, Hungary

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Budapest, , Hungary

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Nyíregyháza, , Hungary

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Veszprém, , Hungary

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Hyderabad, Andhra Pradesh, India

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Bangalore, Karnataka, India

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Kochi, Kerala, India

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Nashik, Maharashtra, India

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New Delhi, National Capital Territory of Delhi, India

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Jaipur, Rajasthan, India

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Madurai, Tamil Nadu, India

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Vellore, Tamil Nadu, India

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Kolkata, West Bengal, India

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Delhi, , India

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Mumbai, , India

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Dublin, , Ireland

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Ancona, AN, Italy

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Bergamo, BG, Italy

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Genova, GE, Italy

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Monza, MB, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Rozzano, MI, Italy

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Perugia, PG, Italy

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Pisa, PI, Italy

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Aviano, PN, Italy

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Parma, PR, Italy

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Reggio Emilia, RE, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Orbassano, TO, Italy

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Udine, UD, Italy

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Napoli, , Italy

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Nagoya, Aichi-ken, Japan

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Kashiwa, Chiba, Japan

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Akashi, Hyōgo, Japan

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Hirakata, Osaka, Japan

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Osaka, Osaka, Japan

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Koto Ku, Tokyo, Japan

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Niigata, , Japan

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El Achrafiyé, , Lebanon

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Saida, , Lebanon

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Guadalajara, Jalisco, Mexico

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Leiden, South Holland, Netherlands

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Amersfroort, , Netherlands

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Enschede, , Netherlands

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Groningen, , Netherlands

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Groningen, , Netherlands

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Maastricht, , Netherlands

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Zoetermeer, , Netherlands

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Oslo, , Norway

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Szczecin, , Poland

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Warsaw, , Poland

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Saint Petersburg, , Russia

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Singapore, , Singapore

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Bundang Gu, Gyeonggi-do, South Korea

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Gyeonggi-do, Korea, South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Granada, Andalusia, Spain

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Málaga, Andalusia, Spain

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Seville, Andalusia, Spain

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Seville, Andalusia, Spain

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Palma de Mallorca, Balearic Islands, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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L'Hospitalet de Llobregat, Catalonia, Spain

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Lleida, Catalonia, Spain

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Mataró, Catalonia, Spain

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Reus, Catalonia, Spain

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Badajoz, Extremadura, Spain

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A Coruña, Galicia, Spain

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Lugo, Galicia, Spain

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Pamplona, Navarre, Spain

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Oviedo, Principality of Asturias, Spain

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San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

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Alicante, Valencia, Spain

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Valencia, Valencia, Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Linköping, , Sweden

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Lund, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Songkhla, Hat Yai, Thailand

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Khon Kaen, THA, Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Exeter, Devon, United Kingdom

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Leeds, West Yorkshire, United Kingdom

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Birmingham, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Nottingham, , United Kingdom

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Countries

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Argentina Australia Austria Brazil China Colombia Denmark France Germany Greece Hungary India Ireland Italy Japan Lebanon Mexico Netherlands Norway Poland Russia Singapore South Korea Spain Sweden Taiwan Thailand Turkey (Türkiye) United Kingdom

References

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Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. doi: 10.1016/S0140-6736(17)30123-X. Epub 2017 Jan 24.

Reference Type DERIVED
PMID: 28126333 (View on PubMed)

Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.

Reference Type DERIVED
PMID: 27130468 (View on PubMed)

Other Identifiers

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2013-000319-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLDK378A2301

Identifier Type: -

Identifier Source: org_study_id

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