Clinical trial NCT02450903: LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.
Official title: A Phase II, Multi-center, Open-label, Single-Arm Study to Evaluate the Efficacy and Safety of Oral LDK378 Treatment for Patients With ALK-Positive Non-Small Cell Lung Cancer Previously Treated With Alectinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small-Cell Lung Cancer
Keywords: Non-Small-Cell Lung Cancer
NSCLC
ALK
LDK378
alectinib
Non-small cell lung carcinoma (NSCLC)
lung cancer
lung adenocarcinoma
Non small cell lung carcinoma
Non small cell lung cancer
Non-small cell lung cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-05-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a single-arm, open-label, multicenter, phase II study to evaluate the efficacy and safety of the ALK inhibitor LDK378 when used as single agent in patients with ALK-rearranged stage IIIB or IV NSCLC previously treated with alectinib. Treatment with LDK378 750 mg qd continued until the patient experienced disease progression as determined by the investigator according to RECIST 1.1, unacceptable toxicity that precluded further treatment, pregnancy, start of a new anticancer therapy, discontinued treatment at the discretion of the patient or investigator, lost to follow-up, death, or study was terminated by Sponsor.

Detailed description: Study completed as per protocol. 'Switched to commercial drug' implies that after the primary and secondary objectives were achieved, one patient continued the study treatment as they did not meet the progression disease or AE to be discontinued from the treatment. But after the regulatory approval, Novartis decided to close the study, the 1 patient switched to commercially available drug.

Eligibility criteria: Key Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of Stage IIIb or IV NSCLC that carries an ALK rearrangement as determined locally by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test.
* Patients must have NSCLC that has progressed at study enrollment.
* Patients must have received previous treatment with alectinib for treatment of locally advanced or metastatic NSCLC. Prior therapy with crizotinib as ALK inhibitor therapy in addition to alectinib is allowed. Alectinib doesn't need to be the last therapy prior to study enrollment. No particular sequence of prior alectinib and crizotinib is required for enrollment.
* Patients must be chemotherapy-naïve or have received only one line of prior cytotoxic chemotherapy.
* Age 18 years or older at the time of informed consent.

Key Exclusion Criteria:

* Patients with known hypersensitivity to any of the excipients of LDK378.
* Prior therapy with other ALK inhibitor investigational agents except crizotinib and alectinib.
* Prior systemic anti-cancer (including investigational) therapy aside from alectinib, crizotinib and one regimen of previous cytotoxic chemotherapy for locally advanced or metastatic NSCLC.
* Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
* Patient with history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
* Patients with history of carcinomatous meningitis.
* Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
* Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)

Primary outcomes:
measure: Overall Response Rate (ORR) to LDK378 by Investigator Assessment
timeFrame: Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 6 cycles of 28 days up to 798 days
measure: Time to Tumor Response (TTR)
timeFrame: 6 cycles of 28 days up to 798 days
measure: Duration of Response (DOR)
timeFrame: 6 cycles of 28 days up to 798 days
measure: Progression Free Survival (PFS)
timeFrame: 6 cycles of 28 days up to 798 days
measure: Overall Survival (OS)
timeFrame: 6 cycles of 28 days up to 798 days
measure: Overall Intracranial Response Rate (OIRR)
timeFrame: 6 cycles of 28 days up to 798 days
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sakyo Ku
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Natori
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Osaka Sayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hida T, Seto T, Horinouchi H, Maemondo M, Takeda M, Hotta K, Hirai F, Kim YH, Matsumoto S, Ito M, Ayukawa K, Tokushige K, Yonemura M, Mitsudomi T, Nishio M. Phase II study of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND-9. Cancer Sci. 2018 Sep;109(9):2863-2872. doi: 10.1111/cas.13721. Epub 2018 Jul 25.