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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Doublet) and Crizotinib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01828112
• Other study ID #: CLDK378A2303
• Secondary ID: 2012-005637-36
• Status: Completed
• Phase: Phase 3
• Start date: June 28, 2013
• Est. completion date: November 10, 2023

Study information

• Verified date: November 2023
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 231
• Est. completion date: November 10, 2023
• Est. primary completion date: January 26, 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-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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ceritinib
Ceritinib is the investigational treatment and is referred to as the investigational study drug and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.
• pemetrexed
Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m2 every 21 days.
• docetaxel
Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m2 every 21 days.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Besancon cedex
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Le Mans	Cedex 09
France	Novartis Investigative Site	Marseille cedex 20	Bouches Du Rhone
France	Novartis Investigative Site	Mulhouse cedex
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Suresnes
Germany	Novartis Investigative Site	Bad Berka
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Esslingen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Tuebingen
Germany	Novartis Investigative Site	Ulm
Hong Kong	Novartis Investigative Site	Hong Kong
Ireland	Novartis Investigative Site	Dublin 4
Ireland	Novartis Investigative Site	Limerick	Co Limerick
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Avellino	AV
Italy	Novartis Investigative Site	Aviano	PN
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Monza	MB
Italy	Novartis Investigative Site	Orbassano	TO
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	Verona	VR
Japan	Novartis Investigative Site	Akashi	Hyogo
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
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	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka Sayama	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Takatsuki-city	Osaka
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Ashrafieh
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Groningen
Portugal	Novartis Investigative Site	Lisboa
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow Region Istra Village
Russian Federation	Novartis Investigative Site	Saint Petersburg
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Cataluña
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	Madrid	Andalucia
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Luzern
Switzerland	Novartis Investigative Site	St. Gallen
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Pendik Istanbul
United Kingdom	Novartis Investigative Site	Aberdeen
United Kingdom	Novartis Investigative Site	Cheltenham	Gloucestershire
United Kingdom	Novartis Investigative Site	Hants	Southampton
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Fairfax	Virginia
United States	Novartis Investigative Site	Fayetteville	Arkansas
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Iowa City	Iowa
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Maywood	Illinois
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sugar Land	Texas
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Hong Kong,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Netherlands,  Portugal,  Russian Federation,  Singapore,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC)	PFS is 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	Overall Survival (OS)	OS is defined as time from date of randomization to date of death due to any cause.	Month 18
Secondary	Overall Response Rate (ORR)	ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)	Month 18
Secondary	Duration of Response (DOR)	DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer	Month 18
Secondary	Disease Control Rate (DCR)	DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)	Month 18
Secondary	Time to Response (TTR)	TTR is defined as the time from date of randomization to date of first documented response (CR or PR)	Month 18
Secondary	Patient Reported Outcomes (PRO)		Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Secondary	Time to Definitive Deterioration		from the date of randomization to the date of event for disease related symptoms
Secondary	Overall Intracranial Response Rate (OIRR)	OIRR is defined as the ORR based on lesions in brain (target, nontarget lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall confirmed response of CR or PR in the brain per modified RECIST 1.1* as assessed by BIRC neuroradiologist.	Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Secondary	Intracranial Disease Control Rate (IDCR)	IDCR is defined as the DCR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall response of CR or PR or SD (or non-CR/nonPD) in the brain per modified RECIST 1.1* as assessed by BIRC neuro-radiologist.	Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks
Secondary	Duration of Intracranial Response (DOIR)	DOIR is defined as the DOR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated from the time of first documented response of CR or PR to the date of the first documented disease progression in the brain or death due to any cause per modified RECIST 1.1* as assessed by BIRC neuro-radiologist.	Screening, followed by every 6 weeks until Month 18 after Month 18 every 9 weeks