Ceritinib Rare Indications Study in ALK+ Tumors

NCT02465528 | Terminated Phase 2 Results

• 1 other identifier: CLDK378A2407
• Study Type: interventional
• Target: 22
• Locations: 8 countries
• Sites: 14

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).

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• 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

• 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

• 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

• Percent of Participant Deaths During Treatment and Follow-up

  Baseline up to approximately 84 weeks

Study Arms (4)

Inflammatory myofibroblastic tumor (IMT)

EXPERIMENTAL

Patients diagnosed with IMT with a confirmed translocation involving the ALK gene

Drug: Ceritinib (LDK378)

Anaplastic large cell lymphoma (ALCL)

EXPERIMENTAL

Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive

Drug: Ceritinib (LDK378)

Glioblastoma (GBM)

EXPERIMENTAL

Patients with GBM with a translocation involving the ALK gene

Drug: Ceritinib (LDK378)

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).

Drug: Ceritinib (LDK378)

Interventions

Ceritinib (LDK378) DRUG

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.

Anaplastic large cell lymphoma (ALCL); Any other ALK-positive tumor; Glioblastoma (GBM); Inflammatory myofibroblastic tumor (IMT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Novartis Investigative Site

Brno, Czech Republic, 656 53, Czechia

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Saint-Herblain Cédex, 44805, France

Location

Novartis Investigative Site

Strasbourg, F 67085, France

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Granuloma, Plasma Cell; Glioblastoma; Hematologic Neoplasms

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Granuloma; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms by Site; Hematologic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

888-669-6682

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 29, 2015
• First Posted: June 8, 2015
• Study Start: May 6, 2016
• Primary Completion: August 20, 2018
• Study Completion: August 20, 2018
• Last Updated: December 27, 2019
• Results First Posted: October 21, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); DK (1); IL (1); IT (1); FR (3); KR (3); ES (2); TH (2)