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An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

Primary Purpose

Non-small Cell Lung Cancer (NSCLC)

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

LDK378

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring non-small cell lung cancer (NSCLC)

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with histologically or cytologically confirmed, unresectable NSCLC that carries a ROS1 rearrangement, as per FISH assay (Abbott Molecular Inc.)
ECOG performance status of 0 to 2
Male or female; ≥ 20 years of age
Subjects must have received at least 1 platinum doublet to treat their locally advanced or metastatic NSCLC
Subjects whose disease has progressed within 6 months Subjects with measurable lesion (using RECIST 1.1 criteria)
Subjects must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2
Subjects must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since
Provision of written informed consent prior to any study specific procedures

Exclusion Criteria:

Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy.
Any major operation or irradiation within 4 weeks of baseline disease assessment
Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
Subjects 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
Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ or treated thyroid cancer.
Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension)
Pregnant or lactating female
Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Sites / Locations

Yonsei Cancer Center at Yonsei University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LDK378 arm

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate (ORR)

Lesions measurements are performed by CT or MRI scan, evaluation by RECIST criteria v1.1

Secondary Outcome Measures

Full Information

NCT ID

NCT01964157

First Posted

October 9, 2013

Last Updated

January 9, 2019

Sponsor

Yonsei University

1. Study Identification

Unique Protocol Identification Number

NCT01964157

Brief Title

An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Unknown status

Study Start Date

September 1, 2013 (Actual)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yonsei University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

ROS1 is a receptor tyrosine kinase with constitutive kinase activity. ROS1 was previously discovered in cell lines where ROS1 fused with other proteins to act as a driver oncogene. In 2007, Rikova et al reported ROS1 fusion as driver mutations in NSCLC cell line (HCC78; SLC34A2-ROS1) and NSCLC patient (CD74-ROS1). Li et al also found about 1% of samples harboring CD74-ROS1 fusion in 202 resected lung adenocarcinomas from never smokers. The incidence was as high as 10% in East Asian population. Currently there are now at least 13 ROS1 fusion variants involving 8 fusion partners (CD74-, SLC34A2-, FIG-, TPM3-, SDC4-, LRIG3-, ERZ-, KDERL2-) identified in ROS1 positive NSCLC. LDK378 is an orally highly selective and potent ALK kinase inhibitor. In preclinical studies, LDK378 has much lower IC50 values than crizotinib in cell lines engineered to express ROS1 rearrangement (0.15 nM versus 3 nM) and is approximately 20-fold more potent. LDK378 is a potent inhibitor of tumor growth in rodent models of both ALCL and NSCLC. We suggest a phase II trial of LDK378 in advanced non-small cell lung cancer patients with ROS1 rearrangement. The aim of current trial is to evaluate the antitumor efficacy and safety profile of LDK378 and to identify biomarker to predict the tumor response to LDK378.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer (NSCLC)

Keywords

non-small cell lung cancer (NSCLC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

LDK378 arm

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

LDK378

Intervention Description

LDK378 750mg oral administration and continuously (28-day treatment schedule as one treatment cycle)

Primary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

Lesions measurements are performed by CT or MRI scan, evaluation by RECIST criteria v1.1

Time Frame

1 month after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with histologically or cytologically confirmed, unresectable NSCLC that carries a ROS1 rearrangement, as per FISH assay (Abbott Molecular Inc.) ECOG performance status of 0 to 2 Male or female; ≥ 20 years of age Subjects must have received at least 1 platinum doublet to treat their locally advanced or metastatic NSCLC Subjects whose disease has progressed within 6 months Subjects with measurable lesion (using RECIST 1.1 criteria) Subjects must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2 Subjects must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since Provision of written informed consent prior to any study specific procedures Exclusion Criteria: Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy. Any major operation or irradiation within 4 weeks of baseline disease assessment Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug Subjects 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 Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ or treated thyroid cancer. Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension) Pregnant or lactating female Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Byung Chul Cho, MD

Phone

82-2-2228-0880

CBC1971@yuhs.ac

Facility Information:

Facility Name

Yonsei Cancer Center at Yonsei University Medical Center

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Byung Chul Cho, M.D., Ph.D.

Phone

82-2-2228-0880

CBC1971@yuhs.ac

12. IPD Sharing Statement

Learn more about this trial

An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

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