Clinical Trials/NCT02465528

NCT02465528

Terminated

Phase 2

A Phase II, Open Label, Multi-center, Multi-arm Study of Ceritinib in Patients With Advanced Solid Tumors and Hematological Malignancies Characterized by Genetic Abnormalities of Anaplastic Lymphoma Kinase (ALK)

Novartis Pharmaceuticals1 site in 1 country22 target enrollmentMay 6, 2016

ConditionsTumors With Aberrations in ALK Anaplastic Large Cell Lymphoma Inflammatory Myofibroblastic Tumor Glioblastoma

InterventionsCeritinib (LDK378)

DrugsCeritinib (LDK378)

Overview

Phase: Phase 2
Intervention: Ceritinib (LDK378)
Conditions: Tumors With Aberrations in ALK
Sponsor: Novartis Pharmaceuticals
Enrollment: 22
Locations: 1
Primary Endpoint: Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment
Status: Terminated
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is Proof-of-Concept (POC) study to assess the preliminary antitumor activity and safety and tolerablity using ceritinib (LDK378) in the treatment of life threatening tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases).

Registry

clinicaltrials.gov

Start Date

May 6, 2016

End Date

August 20, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patient has a histologically or cytologically confirmed diagnosis of ALK positive (ALK+) tumor other than Non-Small Cell Lung Cancer (NSCLC).
•Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory.
•Patient has WHO Performance Status (PS) ≤ 2
•Patient must have received at least one line of prior systemic treatment for recurrent, locally advanced and/or metastatic disease, and may have discontinued for:
•Disease progression as defined by RECIST 1.1 for solid tumors; by RANO for GBM and by Cheson assessment criteria for lymphoma, or
•Intolerance described as any discontinuation due to an AE of any grade despite appropriate supportive treatment
•Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
•Patient has received no chemotherapy, immunotherapy or stem cell therapy at least 4 weeks before starting ceritinib
•Radiotherapy and prior ALK inhibitors must be stopped at least 1 week prior to starting ceritinib
•Recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] v4.03).

Exclusion Criteria

•Patient has ALK+lung cancer
•Patient with symptomatic 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 acute or chronic GI disease that may significantly alter the absorption of ceritinib.
•Patient with a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
•Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
•Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months).
•Patient has evidence of active viral hepatitis, including Hepatitis A, B or C (testing for viral hepatitis is not mandatory).
•Patient has known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).

Arms & Interventions

Inflammatory myofibroblastic tumor (IMT)

Patients diagnosed with IMT with a confirmed translocation involving the ALK gene

Intervention: Ceritinib (LDK378)

Anaplastic large cell lymphoma (ALCL)

Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive

Intervention: Ceritinib (LDK378)

Glioblastoma (GBM)

Patients with GBM with a translocation involving the ALK gene

Intervention: Ceritinib (LDK378)

Any other ALK-positive tumor

Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2).

Intervention: Ceritinib (LDK378)

Outcomes

Primary Outcomes

Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment

Time Frame: Baseline up to approximately 16 weeks

The DCR is defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks from the start of ceritinib treatment. The assessment criteria are: Solid Tumors (RECIST 1.1., Response Evaluation Criteria in Solid Tumors); GBM (RECIST 1.1 and RANO, Response Evaluation in Neuro-Oncology); Hematologic tumors (Cheson).

Secondary Outcomes

Overall Response Rate (ORR) Per Investigator Assessment(Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks)
Duration of Response (DOR) Per Investigator Assessment(Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks)
Time to Response (TTR) Per Investigator Assessment(Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks)
Progression Free Survival (PFS) Per Investigator Assessments(Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks)
Percent of Participant Deaths During Treatment and Follow-up(Baseline up to approximately 84 weeks)