Clinical trial NCT02465528: Ceritinib Rare Indications Study in ALK+ Tumors
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Tumors With Aberrations in ALK
Anaplastic Large Cell Lymphoma
Inflammatory Myofibroblastic Tumor
Glioblastoma
Keywords: ALK
GBM
hematological malignancy
anaplastic lymphoma kinase
glioblastoma
anaplastic large cell lymphoma
IMT
inflammatory myofibroblastic tumor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-06-08
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Depending on the tumor type, subjects were to be enrolled into one of the following parallel arms: ALCL (anaplastic large cell lymphoma); IMT (inflammatory myofibroblastic tumor); glioblastoma (GBM), and any other ALK+ tumor. If there were 5 or more subjects of the same tumor type in the "Any other ALK+ tumor" arm, then a separate arm was to be opened for that specific tumor type.
Primary purpose: TREATMENT

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).


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).

Primary outcomes:
measure: Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment
timeFrame: Baseline up to approximately 16 weeks
Secondary outcomes:
measure: Overall Response Rate (ORR) Per Investigator Assessment
timeFrame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks
measure: Duration of Response (DOR) Per Investigator Assessment
timeFrame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
measure: Time to Response (TTR) Per Investigator Assessment
timeFrame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
measure: Progression Free Survival (PFS) Per Investigator Assessments
timeFrame: Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks
measure: Percent of Participant Deaths During Treatment and Follow-up
timeFrame: Baseline up to approximately 84 weeks
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
Study officials:
References: