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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01828099
• Other study ID #: CLDK378A2301
• Secondary ID: 2013-000319-26
• Status: Completed
• Phase: Phase 3
• Start date: July 9, 2013
• Est. completion date: January 7, 2024

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study was to compare the antitumor activity of LDK378 versus reference chemotherapy. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 376
• Est. completion date: January 7, 2024
• Est. primary completion date: June 24, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories.

2. Patient has newly diagnosed stage IIIB (who are 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 exception of neo-adjuvant or adjuvant therapy

3. Patient has at least one measurable lesion as defined by RECIST 1.1.

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 platinum containing drugs, pemetrexed 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Ceritinib
Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. Ceritinib (LDK378) was the investigational treatment and is referred to as the investigational study treatment/drug.
• Pemetrexed
Pemetrexed was administered at a dose of 500 mg/m2 as an iv infusion on Day 1 of each 21-day cycle to patients randomized to the chemotherapy arm.
• Cisplatin
Cisplatin was administered by IV at a dose of 75 mg/m2 every 21 days for up to 4 cycles.
• Carboplatin
Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Auckland
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Wien
Brazil	Novartis Investigative Site	Barretos	SP
Brazil	Novartis Investigative Site	Itajai	SC
Brazil	Novartis Investigative Site	Natal	RN
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Guang Dong Province
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Shanghai	Shanghai
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	XI An	Shanxi
Colombia	Novartis Investigative Site	Monteria
Denmark	Novartis Investigative Site	Herlev
Denmark	Novartis Investigative Site	Odense C
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Limoges Cedex
France	Novartis Investigative Site	Paris 10
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Rennes
France	Novartis Investigative Site	Strasbourg Cedex
France	Novartis Investigative Site	Toulon Cedex 9	Val De Marne
France	Novartis Investigative Site	Villejuif
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Tuebingen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wiesbaden
Greece	Novartis Investigative Site	Heraklion Crete
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Delhi
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Mumbai
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Vellore	Tamil Nadu
Ireland	Novartis Investigative Site	Dublin 4
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Aviano	PN
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Monza	MB
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Perugia	PG
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Reggio Emilia	RE
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Udine	UD
Japan	Novartis Investigative Site	Akashi	Hyogo
Japan	Novartis Investigative Site	Hirakata-city	Osaka
Japan	Novartis Investigative Site	Kashiwa	Chiba
Japan	Novartis Investigative Site	Koto ku	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Osaka-city	Osaka
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Saida
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Leiden
Netherlands	Novartis Investigative Site	Maastricht	AZ
Norway	Novartis Investigative Site	Oslo
Poland	Novartis Investigative Site	Szczecin
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Badajoz	Extremadura
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Reus	Tarragona
Spain	Novartis Investigative Site	Sevilla	Andalucia
Sweden	Novartis Investigative Site	Linkoping
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uppsala
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Kuei Shan Chiang	Taoyuan
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung City
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
Turkey	Novartis Investigative Site	Ankara	Sihhiye
Turkey	Novartis Investigative Site	Istanbul
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Leeds	West Yorkshire
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Austria,  Brazil,  China,  Colombia,  Denmark,  France,  Germany,  Greece,  India,  Ireland,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Mexico,  Netherlands,  Norway,  Poland,  Russian Federation,  Singapore,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)	PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of 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 (assessed every 6 weeks up to approximately 34 months)
Secondary	Overall Survival (OS)	OS defined as time from date of randomization to date of death due to any cause	From randomization until death (up to approximately 34 months)
Secondary	Overall Response Rate (ORR)	ORR defined as the proportion of patients with a best overall response defined as Complete Response (CR) or Partial Response (PR) as evaluated by Blinded Independent Review Committee (BIRC) and by investigator assessment per RECIST 1.1	From randomization until death (up to approximately 34 months)
Secondary	Duration of Response (DOR)	DOR defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause	From randomization until death (up to approximately 34 months)
Secondary	Disease Control Rate (DCR)	DCR defined as the proportion of patients with best overall response of CR, PR, or Stable Disease (SD)	From randomization until death (up to approximately 34 months)
Secondary	Time to Response (TTR)	TTR defined as the time from date of randomization to date of first documented response (CR or PR)	From randomization until death (up to approximately 34 months)
Secondary	Patient Reported Outcomes	The time to definitive deterioration from the date of randomization to the date of event for disease related symptoms.	Screening, followed by every 6 weeks until Month 33 after Month 33 every 9 weeks.