Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase II Study to Evaluate the Efficacy and Safety of Oral Ceritinib in Patients With ALK-positive NSCLC Metastatic to the Brain and/or to Leptomeninges (Ascend-7)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02336451
Recruitment Status : Recruiting
First Posted : January 13, 2015
Last Update Posted : February 25, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a phase II, multi-center, open-label, five-arm study in which the efficacy and safety of oral ceritinib treatment will be assessed in patients with NSCLC metastatic to the brain and/or to leptomeninges harboring a confirmed ALK rearrangement, 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.

Condition or disease Intervention/treatment Phase
ALK-positive Non-small Cell Lung Cancer Drug: LDK378 Phase 2

Detailed Description:

Approximately 160 patients diagnosed with ALK-positive metastatic NSCLC (according to the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual) and active lesions in the brain and/or diagnosed with leptomeningeal carcinomatosis will be included in the study, approximately 40 patients in Arm 1 and Arm 2, approximately 30 patients in Arms 3 and Arm 4, and approximately 20 patients in Arm 5. Additional patients may be enrolled in Arm 4 to achieve approximately 60 patients in Arms 3 and 4 together (i.e. ALKi naïve patients), if enrollment rate in Arm 3 is slow.

  • Arm 1 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain and with prior exposure to an ALKi.
  • Arm 2 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain but with prior exposure to an ALKi.
  • Arm 3 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain but with no prior exposure to an ALKi.
  • Arm 4 will include patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain and with no prior exposure to an ALKi
  • Arm 5 will include any patients with leptomeningeal carcinomatosis with or without evidence of active lesion at the baseline Gadoliniumenhanced brain MRI. Note: Previous treatment with ALK inhibitors other than crizotinib is not allowed in Arms 1, 2, and 5.

Ceritinib will be administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule. The treatment period will start on Cycle 1 Day 1.

Complete tumor assessments including gadolinium enhanced brain MRI will be repeated at Week 8 (on Cycle 3 Day 1) and every 8 weeks (i.e. every 2 cycles) thereafter or earlier if clinically indicated. Safety evaluations will include (S)AEs, physical examination, vital signs, ECGs, laboratory parameters and WHO performance status. Blood and CSF samples for PK will also be collected.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : April 1, 2015
Estimated Primary Completion Date : February 14, 2019
Estimated Study Completion Date : February 14, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ceritinib

Arm Intervention/treatment
Experimental: LDK378
LDK378 will be administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule. The treatment period will start on Cycle 1 Day 1.
Drug: LDK378
LDK378 (ceritinib) 750 mg once daily, orally administered
Other Name: Ceritinib




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 24 weeks ]
    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 Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: 24 weeks ]
    The DCR is defined as the proportion of patients with a best overall response of CR, PR or SD in the whole body, as assessed per RECIST 1.1 by the investigator.

  2. Overall Intracranial Response Rate (OIRR) per modified RECIST 1.1 [ Time Frame: 24 weeks ]
    • Overall Intracranial Response Rate (OIRR) by Investigator and BIRC for patients with measurable brain metastases at baseline

  3. Intracranial Disease Control Rate (IDCR) per modified RECIST 1.1 [ Time Frame: 8 and 16 weeks ]
    Intracranial Disease Control Rate (IDCR) at 24 weeks and overall by Investigator and BIRC

  4. Time to intracranial tumor response (TTIR) per modified RECIST 1.1 [ Time Frame: 24 weeks ]
    Time to intracranial tumor response (TTIR) by Investigator and BIRC for patients with measurable brain metastases at baseline

  5. Duration of intracranial response (DOIR) per modified RECIST 1.1 [ Time Frame: 24 weeks ]
    Duration of intracranial response (DOIR) by Investigator and BIRC for patients with measurable brain metastases at baseline

  6. Overall Extracranial Response Rate (OERR) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Overall Extracranial Response Rate (OERR) by Investigator and BIRC

  7. Extracranial Disease Control Rate (EDCR) per RECIST 1.1 [ Time Frame: 8 and 16 weeks ]
    Extracranial Disease Control Rate (EDCR) at 24 weeks by Investigator and BIRC

  8. Time to extracranial tumor response (TTER) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Time to extracranial tumor response (TTER) by Investigator and BIRC

  9. Duration of extracranial response (DOER) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Duration of extracranial response (DOER) by Investigator and BIRC

  10. Overall response rate (ORR) (whole body) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Overall response rate (ORR) by BIRC

  11. Disease control rate (DCR) (whole body) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Disease control rate (DCR) by BIRC

  12. Time to tumor response (TTR) (whole body) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Time to tumor response (TTR) by Investigator and BIRC

  13. Duration of response (DOR) (whole body) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Duration of response (DOR) by Investigator by BIRC

  14. Progression free survival (PFS) (whole body) per RECIST 1.1 [ Time Frame: 24 weeks ]
    Progression free survival (PFS) by Investigator by BIRC

  15. Overal survival [ Time Frame: 24 weeks ]
    Overal survival (OS)

  16. Overall Safety [ Time Frame: 24 weeks ]
    AEs, ECGs and laboratory abnormalities

  17. Pharmacokinetics of ceritinib in study population [ Time Frame: 24 weeks ]
    Cmax on C2D1 and Cmin concentrations of ceritinib in plasma.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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.
  • 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.
  • 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.
  • Patient has life expectancy ≥ 6 weeks.
  • Patient has a WHO performance status 0-2.

Patients in Arm 1 to 4 must also meet the following inclusion criteria:

- Patients must have active brain metastases from NSCLC, confirmed by Gadolinium-enhanced MRI without concomitant leptomeningeal carcinomatosis. Dose of steroids must be stable for 5 days before the baseline brain MRI.

Patients in Arm 5 must also meet the following inclusion criteria:

- Patients must be diagnosed with leptomeningeal carcinomatosis.

Exclusion Criteria:

  • 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.
  • 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.
  • Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
  • Patient has impairment of GI function or GI disease that may significantly alter the absorption of ceritinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
  • Patient is receiving unstable or increasing doses of corticosteroids.
  • Patient has other severe, acute, or chronic medical conditions including uncontrolled diabetes mellitus or psychiatric conditions or laboratory abnormalities that in the opinion of the investigator may increase the risk associated with study participation, or that may interfere with the interpretation of study results.

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02336451


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

  Show 67 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02336451     History of Changes
Other Study ID Numbers: CLDK378A2205
2014-000578-20 ( EudraCT Number )
First Posted: January 13, 2015    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ALK-positive
NSCLC
brain metastasis
metastatic to the brain and/or to leptomeninges.

Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Ceritinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action