Ceritinib Rare Indications Study in ALK+ Tumors
Condition: Tumors With Aberrations in ALK; Anaplastic Large Cell Lymphoma; Inflammatory Myofibroblastic Tumor; Glioblastoma
MeSH terms: Lymphoma; Neoplasms; Glioblastoma; Lymphoma, Large-Cell, Anaplastic; Granuloma, Plasma Cell
Intervention: Ceritinib (LDK378)
Intervention description: 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.
Intervention MeSH terms: Ceritinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
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.
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ALK; GBM; hematological malignancy; anaplastic lymphoma kinase; glioblastoma; anaplastic large cell lymphoma; IMT; inflammatory myofibroblastic tumor

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).