A clinical study of oral ceritinib in patients with ALK-Positive Non-Small Cell Lung Cancer metastatic to the brain and/or to leptomeninges.

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2014-000578-20-GB
• Date of registration: 20/07/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A clinical study of oral ceritinib in patients with ALK-Positive Non-Small Cell Lung Cancer metastatic to the brain and/or to leptomeninges.
• Scientific title: A phase II, multi-center, open-label, five-arm study to evaluate the efficacy and safety of oral ceritinib treatment for patients with ALK-Positive Non-Small Cell Lung Cancer (NSCLC) metastatic to the brain and/or to leptomeninges
• Date of first enrolment: 31/07/2015
• Target sample size: 84
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000578-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, France, Germany, Hong Kong, Italy, Korea, Democratic People's Republic of, Netherlands, New Zealand, Russian Federation, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharmaceuticals UK Ltd

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharmaceuticals UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1a. Histologically or cytologically confirmed diagnosis of metastatic NSCLC according to the 7th edition of the AJCC Cancer Staging Manual. In addition, the NSCLC must harbor an ALK rearrangement, as assessed using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above is not locally available, a test to confirm ALK rearrangement must be performed by a Novartis designated central laboratory. Patients must wait for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib.
2a. Patients that require ALK rearrangement testing by a Novartis designated central laboratory must have a tumor tissue sample available as an archival sample (if possible obtained after the completion of the patient's last therapeutic regimen) or as a new biopsy. If that is not possible, any tumor biopsy obtained at or since the time of diagnosis can be used (a maximum of two years from biopsy excision is preferred).
3. At least one extracranial measurable lesion as defined by RECIST 1.1.
A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
4. Patient is 18 years of age or older at the time of informed consent.
5. Patients may or may not have neurological symptoms but must:
• Be able to swallow and retain oral medication.
• Be neurologically stable within at least 1 week prior to the first dose of study drug. Neurologically stable is defined as improved or stable neurological examination without increased doses of steroids to manage CNS symptoms within the last 5 days.
6. Patients may have received prior chemotherapy, crizotinib (other ALK inhibitors are not allowed), biologic therapy or other investigational agents. Patients must have recovered from all toxicities related to prior anticancer therapies to grade = 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
• Patients who have been treated with chemotherapy, with biological therapy or other investigational agent must have discontinued the treatment at least 2 weeks (14 days) prior to starting study drug. In case last chemotherapy contains nitrosourea or mitomycin C, the treatment must be discontinued at least 6 weeks prior to the first dose of study drug.
• Patients, if previously treated with crizotinib must discontinue treatment at least 1 week (7 days) prior to the first dose of study drug.
7a. Patient must meet the following laboratory values at the screening visit:
- Absolute Neutrophil Count = 1.5 x 109/L
- Platelets = 75 x 109/L
- Hemoglobin (Hgb) = 8 g/dL
- Serum creatinine < 1.5 mg/dL and /or calculated creatinine clearance (using Cockcroft-Gault formula) = 30 mL/min
- Total bilirubin = 1.5 x ULN except for patients with Gilbert's syndrome who may only be included if total bilirubin = 3.0 x ULN or direct bilirubin = 1.5 x ULN
- Aspartate transaminase (AST) = 3 x ULN, except for patients with liver metastasis, who are only included if AST = 5 x ULN
- Alanine transaminase (ALT) = 3 x ULN, except for patients with liver metastasis, who are only included if ALT = 5 x ULN
- Alkaline phosphatase (ALP) = 5.0 x ULN
- Serum amylase = 2 x ULN
- Serum lipase = ULN
- Fasting plasma glucose = 200 mg/dL (= 11.1 mmol/L)

Other protocol-defined inclusion criteria may apply.
Are the trial subj
Exclusion criteria:
1. Patient with a history of treatment with ceritinib. Patient with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
2. Patients who need whole brain radiation to control the brain metastases. Patients will not be eligible unless treated brain lesions are progressive or new brain lesions are observed since the post whole brain radiation therapy MRI.
3. In case active brain lesions (single or not) require local treatment but other active brain lesions do not and are not treated, patients will be excluded only if the local treatment (neurosurgical treatment or Stereotactic Radiosurgery ) for the brain metastases is conducted within 2 weeks prior to starting study drug. Patients must have recovered from relevant toxicities related to these procedures to grade = 1(CTCAE v 4.03) prior to receiving the first dose of study drug.
4. Planning of any brain local treatment (including but not limited to surgery, stereotactic radiosurgery, whole brain radiation, intrathecal chemotherapy) following the administration of the first dose of study drug.
5. Patient who has received thoracic radiotherapy to lung fields = 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy = 2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions = 2 weeks prior to the first dose of study drug is allowed.
6. Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to the first dose of study drug or has not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can receive study treatment =1 week after the procedure.

Other protocol-defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-small cell lung cancer
MedDRA version: 20.0 Level: LLT Classification code 10024233 Term: Leptomeningeal metastases System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: LLT Classification code 10006128 Term: Brain metastases System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: ceritinib
Product Code: LDK378
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ceritinib
Current Sponsor code: LDK378
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): Overall response rate (ORR), defined as the proportion of patients with a best overall confirmed response of CR or PR in the whole body as assessed per RECIST 1.1 by the investigator.

Secondary Objective: - To evaluate Disease Control Rate (DCR) in patients with ALK-positive
NSCLC metastatic to the brain and/or to leptomeninges based on
investigator assessment per RECIST 1.1
-To evaluate intracranial tumor-response related endpoints as assessed
by investigators and Blinded Independent Review Committee (BIRC)
(using modified RECIST 1.1 criteria)
-To evaluate extracranial tumor-response related endpoints as assessed
by investigators and BIRC (using RECIST 1.1 criteria)
-To evaluate whole body tumor-response related endpoints as assessed
by investigators and BIRC(using RECIST 1.1 criteria)
-To evaluate overall survival (OS) in this patient population
-To evaluate safety in this patient population
-To characterize the PK of Ceritinib in this patient population

Main Objective: The primary objective is to evaluate the antitumor activity of Ceritinib in patients with ALK-positive NSCLC metastatic to the brain and/or to leptomeninges.

Timepoint(s) of evaluation of this end point: Week 8 (on Cycle 3 Day1) and every 8 weeks (i.e. every 2 cycles)

Secondary Outcome(s)

Secondary end point(s): - Disease Control Rate (DCR) in the whole body as assessed per RECIST
1.1 by the Investigator
-The following intracranial endpoints will be evaluated per modified
RECIST 1.1:
*Overall Intracranial Response Rate (OIRR) by Investigator and
BIRC for patients with measurable brain metastases at baseline
*Intracranial Disease Control Rate (IDCR) at 8, 16 weeks and overall
by Investigator and BIRC
*Time to intracranial tumor response (TTIR) by Investigator and
BIRC for patients with measurable brain metastases at baseline
*Duration of intracranial response (DOIR) by Investigator and BIRC
for patients with measurable brain metastases at baseline
-The following extracranial endpoints will be evaluated per RECIST 1.1:
*Overall Extracranial Response Rate (OERR) by Investigator and
BIRC
*Extracranial Disease Control Rate (EDCR) at 8, 16 weeks by
Investigator and BIRC
*Time to extracranial tumor response (TTER) by Investigator and
BIRC
*Duration of extracranial response (DOER) by Investigator and BIRC
-The following whole body tumor-response related endpoints will be
evaluated per RECIST 1.1:
*Overall response rate (ORR) by BIRC
*Disease control rate (DCR) by BIRC
*Time to tumor response (TTR) by Investigator and BIRC
*Duration of response (DOR) by Investigator by BIRC
*Progression free survival (PFS) by Investigator by BIRC
-Overall survival (OS)
-AEs, ECGs, vital signs and laboratory abnormalities
-Cmax on C2D1 and Cmin concentrations of Ceritinib in plasma.

Timepoint(s) of evaluation of this end point: -Week 8 (on Cycle 3 Day1) and every 8 weeks (i.e. every 2 cycles) except for IDCR and EDCR at 24 weeks

Secondary ID(s)

2014-000578-20-ES

CLDK378A2205

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 29/07/2015
Contact:

Results

• Results available: Yes
• Date Posted: 22/02/2020
• Date Completed: 06/02/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000578-20/results