Ceritinib Rare Indications Study in ALK+ Tumors

Phase 2

Terminated

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

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).

Recruitment & 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).

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment	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 Outcome Measures

Name	Time	Method
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	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.
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	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
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	TTR is defined as the time from date of the first dose to date of first documented response (CR or PR)
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	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
Percent of Participant Deaths During Treatment and Follow-up	Baseline up to approximately 84 weeks	Deaths due to any cause during treatment and 30 day follow-up