Description:
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).
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
CLDK378A2407
- NCT ID:
NCT02465528
Conditions
- Tumors With Aberrations in ALK
- Anaplastic Large Cell Lymphoma
- Inflammatory Myofibroblastic Tumor
- Glioblastoma
Interventions
Drug | Synonyms | Arms |
---|
Ceritinib (LDK378) | | Anaplastic large cell lymphoma (ALCL) |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Inflammatory myofibroblastic tumor (IMT) | Experimental | Patients diagnosed with IMT with a confirmed translocation involving the ALK gene | |
Anaplastic large cell lymphoma (ALCL) | Experimental | Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive | |
Glioblastoma (GBM) | Experimental | Patients with GBM with a translocation involving the ALK gene | |
Any other ALK-positive tumor | Experimental | Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2). | |
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).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | 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
Measure: | Overall Response Rate (ORR) Per Investigator Assessment |
Time Frame: | Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks |
Safety Issue: | |
Description: | 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. |
Measure: | Duration of Response (DOR) Per Investigator Assessment |
Time Frame: | Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks |
Safety Issue: | |
Description: | 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 |
Measure: | Time to Response (TTR) Per Investigator Assessment |
Time Frame: | Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks |
Safety Issue: | |
Description: | TTR is defined as the time from date of the first dose to date of first documented response (CR or PR) |
Measure: | Progression Free Survival (PFS) Per Investigator Assessments |
Time Frame: | Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks |
Safety Issue: | |
Description: | 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 |
Measure: | Percent of Participant Deaths During Treatment and Follow-up |
Time Frame: | Baseline up to approximately 84 weeks |
Safety Issue: | |
Description: | Deaths due to any cause during treatment and 30 day follow-up |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- ALK
- GBM
- hematological malignancy
- anaplastic lymphoma kinase
- glioblastoma
- anaplastic large cell lymphoma
- IMT
- inflammatory myofibroblastic tumor
Last Updated
December 27, 2019