Ceritinib Rare Indications Study in ALK+ Tumors

Glioblastoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02465528
• Other study ID #: CLDK378A2407
• Status: Terminated
• Phase: Phase 2
• Start date: May 6, 2016
• Est. completion date: August 20, 2018

Study information

• Verified date: December 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: August 20, 2018
• Est. primary completion date: August 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Anaplastic Large Cell Lymphoma
• Glioblastoma
• Inflammatory Myofibroblastic Tumor
• Lymphoma
• Lymphoma, Large-Cell, Anaplastic
• Neoplasms
• Tumors With Aberrations in ALK

Intervention

Drug:
• Ceritinib (LDK378)
Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

Locations

Country	Name	City	State
Czechia	Novartis Investigative Site	Brno	Czech Republic
Denmark	Novartis Investigative Site	Copenhagen
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Saint-Herblain Cédex
France	Novartis Investigative Site	Strasbourg
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Milano	MI
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Czechia,  Denmark,  France,  Israel,  Italy,  Korea, Republic of,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment	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).	Baseline up to approximately 16 weeks
Secondary	Overall Response Rate (ORR) Per Investigator Assessment	ORR is defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local assessment according to RECIST 1.1, RANO or Cheson hematological criteria.	Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks
Secondary	Duration of Response (DOR) Per Investigator Assessment	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 any cause	Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
Secondary	Time to Response (TTR) Per Investigator Assessment	TTR is defined as the time from date of the first dose to date of first documented response (CR or PR)	Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
Secondary	Progression Free Survival (PFS) Per Investigator Assessments	PFS is defined as the time from the date of first dose of ceritinib to the date of first documented disease progression or death from any cause	Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks
Secondary	Percent of Participant Deaths During Treatment and Follow-up	Deaths due to any cause during treatment and 30 day follow-up	Baseline up to approximately 84 weeks