Clinical Trials List
Protocol NumberCLDK378A2205
NCT Number(ClinicalTrials.gov Identfier)NCT02336451
2015-06-08 - 2019-09-16
Phase II
Terminated3
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
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 metastatic to the brain and/or to leptomeninges
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- Chao-Hua Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- JIN-YUAN SHIH Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- James Chih-Hsin Yang Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- LI-KAI TSAI Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
ALK-Positive Non Small Cell Lung Cancer metastatic to the brain and/or to leptomeninges
Objectives
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 based on whole body overall response rate (ORR), defined
as the proportion of patients with a best overall confirmed response of
complete response (CR) or partial response (PR) in the whole body as
assessed per RECIST 1.1 by the investigator.
The key secondary objective is to evaluate whole body 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
Test Drug
LDK378
Active Ingredient
Ceritinib
Dosage Form
capsule
Dosage
150
Endpoints
Primary Outcome Measures :
1. Overall Response Rate (ORR) Per Investigator Assessment [ Time Frame: 43 months ]
Overall response rate (ORR) is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
1. Overall Response Rate (ORR) Per Investigator Assessment [ Time Frame: 43 months ]
Overall response rate (ORR) is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed & non-target lesions are not in progression or in complete response.
Inclution Criteria
For all patients:
1. 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 at
a Novartis designated central laboratory using the FDA approved Vysis
ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring
algorithm (including positivity criteria). Patients must wait for the central
result of the ALK rearrangement status before initiating treatment with
ceritinib.
2. All patients 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 to send to the Novartis
designated central laboratory. If that is not possible, any tumor biopsy
obtained at or since the time of diagnosis can be used.
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. Note: Enrollment
of patients with only non-measurable brain metastases may be closed in
one or more arms if it is determined that the target for patients with
measurable brain metastases across study arms will not be met.
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, biologic
therapy or other investigational agents including other ALK inhibitors.
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 (except ALK inhibitors) 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 ALK inhibitors (including crizotinib)
must discontinue treatment at least 1 week (7 days) prior to the first
dose of study drug.
7. 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 (usingCockcroft-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 ≤ ULN
˙ Serum lipase ≤ ULN
˙ Fasting plasma glucose ≤ 200 mg/dL (≤ 11.1 mmol/L)
8. Patient must have the following laboratory values within normal limits or
corrected to within normal limits with supplements during screening:
˙ Potassium
˙ Magnesium
˙ Phosphorus
˙ Total calcium (corrected for serum albumin)
9. Patient has life expectancy ≥ 6 weeks.
10. Patient has a WHO performance status 0-2.
11. Patient has the ability to understand and provide signed informed
consent.
12. Willingness and ability to comply with scheduled visits, treatment plans,
laboratory tests and other study procedures.
Patients in Arm 1 to 4 must also meet the following inclusion criteria:
13. 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.
Note: An active brain lesion is a lesion free of any local treatment (like
stereotactic radiosurgery or whole brain radiation). The following lesions
are considered active:
˙ A newly diagnosed brain metastasis in a patient who has never
received treatment to the brain or in a patient with previously treated
brain metastases.
˙ A brain lesion previously treated with whole brain radiation will only
be considered active when there is an unequivocal size increase in
its solid component (cystic component of the lesion is not considered
for progression determination) compared to the first available postradiation radiological evaluation.
˙ An enlarging brain lesion previously treated with SRS will only be
considered active when the nature of the enlargement is clearly
attributed to the tumoral component of the lesion and not to the
radiation effect.
Patients in Arm 5 must also meet the following inclusion criteria:
14. Patients must be diagnosed with leptomeningeal carcinomatosis. The
diagnosis requires the presence of malignant cells detected at the
cytological examination of the cerebrospinal fluid. In case of at least 2
consecutive negative CSF cytology and serious suspicion of
leptomeningeal carcinomatosis, the diagnosis must be supported by
imaging findings typical of LC on the Gadolinium-enhanced MRI of the
brain or spine.
1. 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 at
a Novartis designated central laboratory using the FDA approved Vysis
ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring
algorithm (including positivity criteria). Patients must wait for the central
result of the ALK rearrangement status before initiating treatment with
ceritinib.
2. All patients 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 to send to the Novartis
designated central laboratory. If that is not possible, any tumor biopsy
obtained at or since the time of diagnosis can be used.
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. Note: Enrollment
of patients with only non-measurable brain metastases may be closed in
one or more arms if it is determined that the target for patients with
measurable brain metastases across study arms will not be met.
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, biologic
therapy or other investigational agents including other ALK inhibitors.
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 (except ALK inhibitors) 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 ALK inhibitors (including crizotinib)
must discontinue treatment at least 1 week (7 days) prior to the first
dose of study drug.
7. 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 (usingCockcroft-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 ≤ ULN
˙ Serum lipase ≤ ULN
˙ Fasting plasma glucose ≤ 200 mg/dL (≤ 11.1 mmol/L)
8. Patient must have the following laboratory values within normal limits or
corrected to within normal limits with supplements during screening:
˙ Potassium
˙ Magnesium
˙ Phosphorus
˙ Total calcium (corrected for serum albumin)
9. Patient has life expectancy ≥ 6 weeks.
10. Patient has a WHO performance status 0-2.
11. Patient has the ability to understand and provide signed informed
consent.
12. Willingness and ability to comply with scheduled visits, treatment plans,
laboratory tests and other study procedures.
Patients in Arm 1 to 4 must also meet the following inclusion criteria:
13. 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.
Note: An active brain lesion is a lesion free of any local treatment (like
stereotactic radiosurgery or whole brain radiation). The following lesions
are considered active:
˙ A newly diagnosed brain metastasis in a patient who has never
received treatment to the brain or in a patient with previously treated
brain metastases.
˙ A brain lesion previously treated with whole brain radiation will only
be considered active when there is an unequivocal size increase in
its solid component (cystic component of the lesion is not considered
for progression determination) compared to the first available postradiation radiological evaluation.
˙ An enlarging brain lesion previously treated with SRS will only be
considered active when the nature of the enlargement is clearly
attributed to the tumoral component of the lesion and not to the
radiation effect.
Patients in Arm 5 must also meet the following inclusion criteria:
14. Patients must be diagnosed with leptomeningeal carcinomatosis. The
diagnosis requires the presence of malignant cells detected at the
cytological examination of the cerebrospinal fluid. In case of at least 2
consecutive negative CSF cytology and serious suspicion of
leptomeningeal carcinomatosis, the diagnosis must be supported by
imaging findings typical of LC on the Gadolinium-enhanced MRI of the
brain or spine.
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.
7. 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.
8. Patient has clinically significant, uncontrolled heart disease and/or recent
cardiac event (within 6 months), such as:
˙ Unstable angina within 6 months prior to screening.
˙ Myocardial infarction within 6 months prior to screening.
˙ History of documented congestive heart failure (New York Heart
Association functional classification III-IV).
˙ Uncontrolled hypertension defined by a Systolic Blood Pressure
(SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100
mm Hg, with or without anti- hypertensive medication. Initiation or
adjustment of antihypertensive medication (s) is allowed prior to
screening.
˙ Ventricular arrhythmias.
˙ Supraventricular and nodal arrhythmias not controlled with
medication.
˙ Other cardiac arrhythmia not controlled with medication.
˙ Corrected QT (QTcF) > 470 ms using Fridericia’s correction on the
screening ECG.
9. 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).
10. Patient receiving treatment with medications that meet one of the
following criteria and that cannot be discontinued at least 1 week prior to
the start of treatment with ceritinib and for the duration of the study :
˙ Strong inhibitors or strong inducers of CYP3A4/5.
˙ Medications with a low therapeutic index that are primarily
metabolized by
˙ CYP3A4/5 and/or CYP2C9.
˙ Medications with a known risk of prolonging the QT interval or
inducing Torsades de Pointes.
11. Patient is currently receiving treatment with warfarin sodium
(Coumadin® ) or any other coumarin-derivative anticoagulants.
12. Patient is receiving unstable or increasing doses of corticosteroids. If
patients are on corticosteroids for endocrine deficiencies or tumorassociated symptoms (non-CNS), dose must have been stabilized (or
decreasing) for at least 5 days before first dose of study treatment. Note:
Dose of steroids must be stable for 5 days before the baseline brain MRI.
13. Patient is receiving treatment with any enzyme-inducing anticonvulsant
that cannot be discontinued at least 1 week before first dose of study
treatment, and for the duration of the study. Patients on non enzymeinducing anticonvulsants are eligible.
14. Patient is pregnant or nursing (lactating) woman, where pregnancy is
defined as the state of a female after conception and until the termination
of gestation, confirmed by a positive hCG laboratory test.
15. Patient is a woman of child-bearing potential, defined as a woman
physiologically capable of becoming pregnant, unless she is using highly
effective contraception during the study and for 3 months after stopping
ceritinib treatment. For female patients treated with reference
chemotherapy highly effective contraception must be used during the
study and for at least 6 months after stopping treatment or as per the
local label.
Highly effective contraception is defined as any of:
˙ Total abstinence: when this is in line with the preferred and usual
lifestyle of the subject. [Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal
are not acceptable methods of contraception].
˙ Female sterilization (have had surgical bilateral oophorectomy with
or without hysterectomy) or tubal ligation at least six weeks before
taking study treatment. In case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by follow
up hormone level assessment.
˙ Male partner sterilization (at least 6 months prior to screening). (With
the appropriate post-vasectomy documentation of the absence of
sperm in the ejaculate). [For female subjects on the study the
vasectomized male partner should be the sole partner for that
patient].
˙ Use of a combination of any two of the following (a+b or a+c or
b+c):
a. Use of oral, injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have
comparable efficacy (failure rate <1%), for example hormonal
vaginal ring or transdermal hormone contraception.
b. Placement of an intrauterine device (IUD) or intrauterine system
(IUS).
c. Barrier methods of contraception: Condom or Occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository.
In case of use of oral contraception, women should have been stable on the
same pill for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g., age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks prior to screening. In the
case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential.
16. Sexually active males unless they use a condom during intercourse while
taking the drug and for 3 months after the last dose of ceritinib treatment.
Male patients should not father a child for 3 months after the last dose of
ceritinib treatment. For male patients treated with reference
chemotherapy they should not father a child for at least 6 months after
the last dose of treatment or as per the local label. A condom is required
to be used also by vasectomized men in order to prevent delivery of the
drug via seminal fluid.
17. 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.
18. Patient has history of interstitial lung disease or interstitial pneumonitis,
including clinically significant radiation pneumonitis (i.e., affecting
activities of daily living or requiring therapeutic intervention).
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.
7. 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.
8. Patient has clinically significant, uncontrolled heart disease and/or recent
cardiac event (within 6 months), such as:
˙ Unstable angina within 6 months prior to screening.
˙ Myocardial infarction within 6 months prior to screening.
˙ History of documented congestive heart failure (New York Heart
Association functional classification III-IV).
˙ Uncontrolled hypertension defined by a Systolic Blood Pressure
(SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100
mm Hg, with or without anti- hypertensive medication. Initiation or
adjustment of antihypertensive medication (s) is allowed prior to
screening.
˙ Ventricular arrhythmias.
˙ Supraventricular and nodal arrhythmias not controlled with
medication.
˙ Other cardiac arrhythmia not controlled with medication.
˙ Corrected QT (QTcF) > 470 ms using Fridericia’s correction on the
screening ECG.
9. 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).
10. Patient receiving treatment with medications that meet one of the
following criteria and that cannot be discontinued at least 1 week prior to
the start of treatment with ceritinib and for the duration of the study :
˙ Strong inhibitors or strong inducers of CYP3A4/5.
˙ Medications with a low therapeutic index that are primarily
metabolized by
˙ CYP3A4/5 and/or CYP2C9.
˙ Medications with a known risk of prolonging the QT interval or
inducing Torsades de Pointes.
11. Patient is currently receiving treatment with warfarin sodium
(Coumadin® ) or any other coumarin-derivative anticoagulants.
12. Patient is receiving unstable or increasing doses of corticosteroids. If
patients are on corticosteroids for endocrine deficiencies or tumorassociated symptoms (non-CNS), dose must have been stabilized (or
decreasing) for at least 5 days before first dose of study treatment. Note:
Dose of steroids must be stable for 5 days before the baseline brain MRI.
13. Patient is receiving treatment with any enzyme-inducing anticonvulsant
that cannot be discontinued at least 1 week before first dose of study
treatment, and for the duration of the study. Patients on non enzymeinducing anticonvulsants are eligible.
14. Patient is pregnant or nursing (lactating) woman, where pregnancy is
defined as the state of a female after conception and until the termination
of gestation, confirmed by a positive hCG laboratory test.
15. Patient is a woman of child-bearing potential, defined as a woman
physiologically capable of becoming pregnant, unless she is using highly
effective contraception during the study and for 3 months after stopping
ceritinib treatment. For female patients treated with reference
chemotherapy highly effective contraception must be used during the
study and for at least 6 months after stopping treatment or as per the
local label.
Highly effective contraception is defined as any of:
˙ Total abstinence: when this is in line with the preferred and usual
lifestyle of the subject. [Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal
are not acceptable methods of contraception].
˙ Female sterilization (have had surgical bilateral oophorectomy with
or without hysterectomy) or tubal ligation at least six weeks before
taking study treatment. In case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by follow
up hormone level assessment.
˙ Male partner sterilization (at least 6 months prior to screening). (With
the appropriate post-vasectomy documentation of the absence of
sperm in the ejaculate). [For female subjects on the study the
vasectomized male partner should be the sole partner for that
patient].
˙ Use of a combination of any two of the following (a+b or a+c or
b+c):
a. Use of oral, injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have
comparable efficacy (failure rate <1%), for example hormonal
vaginal ring or transdermal hormone contraception.
b. Placement of an intrauterine device (IUD) or intrauterine system
(IUS).
c. Barrier methods of contraception: Condom or Occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository.
In case of use of oral contraception, women should have been stable on the
same pill for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if
they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g., age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks prior to screening. In the
case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential.
16. Sexually active males unless they use a condom during intercourse while
taking the drug and for 3 months after the last dose of ceritinib treatment.
Male patients should not father a child for 3 months after the last dose of
ceritinib treatment. For male patients treated with reference
chemotherapy they should not father a child for at least 6 months after
the last dose of treatment or as per the local label. A condom is required
to be used also by vasectomized men in order to prevent delivery of the
drug via seminal fluid.
17. 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.
18. Patient has history of interstitial lung disease or interstitial pneumonitis,
including clinically significant radiation pneumonitis (i.e., affecting
activities of daily living or requiring therapeutic intervention).
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
125 participants
