Ceritinib Rare Indications Study in ALK+ Tumors

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Tumors With Aberrations in ALK, Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumor, Glioblastoma

Intervention / Treatment
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* Drug: Ceritinib (LDK378)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inflammatory myofibroblastic tumor (IMT)<br>Patients diagnosed with IMT with a confirmed translocation involving the ALK gene | Drug: Ceritinib (LDK378)<br>* 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.<br>|
| Experimental: Anaplastic large cell lymphoma (ALCL)<br>Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive | Drug: Ceritinib (LDK378)<br>* 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.<br>|
| Experimental: Glioblastoma (GBM)<br>Patients with GBM with a translocation involving the ALK gene | Drug: Ceritinib (LDK378)<br>* 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.<br>|
| Experimental: Any other ALK-positive tumor<br>Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2). | Drug: Ceritinib (LDK378)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALK, GBM, hematological malignancy, anaplastic lymphoma kinase, glioblastoma, anaplastic large cell lymphoma, IMT, inflammatory myofibroblastic tumor