Clinical Trials List
Protocol NumberCLDK378A2112
NCT Number(ClinicalTrials.gov Identfier)否
2016-01-01 - 2019-12-31
Phase I
Terminated5
ICD-10C34
Malignant neoplasm of bronchus and lung
A multi-center, randomized open label study to assess the systemic exposure, efficacy, and safety of 450 mg ceritinib taken with a low-fat meal and 600 mg ceritinib taken with a low-fat meal as compared with that of 750 mg ceritinib taken in the fasted state in adult patients with ALK rearranged (ALK-positive) metastatic non-small cell lung cancer (NSCLC)
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yu-Min Liao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
5 Terminated
Audit
None
Principal Investigator
Co-Principal Investigator
- kang-Yun LEE Division of Thoracic Medicine
- Tsu-Yi Chao Division of Hematology & Oncology
- Yao-Yu Hsieh Division of Hematology & Oncology
- TSU-YI CHAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Co-Principal Investigator
- Chih-Ming Chou Division of Hematology & Oncology
- Chia-Lun Chang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Principal Investigator
Co-Principal Investigator
- Chien-Ying Liu Division of Thoracic Medicine
- 吳振德 Division of Radiology
- Chih-Hung Chen Division of Thoracic Medicine
- Wen-Cheng Chang Division of Hematology & Oncology
- 林倡葦 Division of Thoracic Medicine
- Chih-Liang Wang Division of Thoracic Medicine
- Shih-Hong Li Division of Thoracic Medicine
- Cheng-Ta Yang Division of Thoracic Medicine
- Chih-Hung Chen Division of Thoracic Medicine
- 李忠恕 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
7 Terminated
Audit
None
Co-Principal Investigator
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
5 Terminated
Condition/Disease
ALK rearranged (ALK-positive) metastatic non-small cell lung cancer (NSCLC)
Objectives
Primary Objective
To assess the steady-state PK of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in patients with metastatic ALK-positive NSCLC.
Secondary Objectives
To assess the antitumor activity, as measured by overall response rate (ORR) and duration of response (DOR) based on Blinded Independent Review Committee (BIRC) assessment, of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in treatment-naive patients with metastatic
ALK-positive NSCLC who have had ALK-positive status determined prospectively at a Novartis central laboratory using the Ventana anti-ALK (D5F3) IHC test (Ventana IHC).
Other Secondary Objectives
To assess the single-dose PK of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in patients with metastatic ALK-positive NSCLC.
Test Drug
LDK378
Active Ingredient
LDK378
Dosage Form
Capusle
Dosage
150
Endpoints
To assess the steady-state PK of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750mg ceritinib taken daily in the fasted state in patients with metastatic ALK-positive NSCLC.
Key secondary
To assess the antitumor activity, as measured by overall response rate (ORR) and duration of response (DOR) based on Blinded Independent Review Committee (BIRC) assessment, of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in treatment-naive patients with metastatic ALK-positive NSCLC who have had ALK-positive status determined prospectively at a Novartis central.
Other Secondary
1. To assess the safety profile (including frequency of patients with GI AEs by severity and overall) of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in patients with metastatic ALK-positive
NSCLC.
2. To assess the single-dose PK of 450 mg or 600 mg ceritinib taken with a low-fat meal as compared with that of 750 mg ceritinib taken in the fasted state in patients with metastatic ALK-positive NSCLC.
3.To assess the antitumor activity of ceritinib as measured by
ORR and DOR by Investigator assessment
TTR, DCR and PFS by BIRC and by Investigator assessment
in treatment-naive patients with metastatic ALK-positive NSCLC who have had ALK-positive status determined centrally by Ventana IHC following oral dosing of 450 mg or 600 mg ceritinib taken daily with a low-fat meal and 750 mg ceritinib taken daily in the fasted state.
4. To assess overall survival (OS) in treatment-naive patients with metastatic ALK-positive NSCLC who have had ALK-positive status determined centrally by Ventana IHC following oral dosing of 450 mg or 600 mg ceritinib taken daily with a low-fat meal and 750 mg ceritinib taken daily in the fasted state.
Key secondary
To assess the antitumor activity, as measured by overall response rate (ORR) and duration of response (DOR) based on Blinded Independent Review Committee (BIRC) assessment, of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in treatment-naive patients with metastatic ALK-positive NSCLC who have had ALK-positive status determined prospectively at a Novartis central.
Other Secondary
1. To assess the safety profile (including frequency of patients with GI AEs by severity and overall) of 450 mg or 600 mg ceritinib taken daily with a low-fat meal as compared with that of 750 mg ceritinib taken daily in the fasted state in patients with metastatic ALK-positive
NSCLC.
2. To assess the single-dose PK of 450 mg or 600 mg ceritinib taken with a low-fat meal as compared with that of 750 mg ceritinib taken in the fasted state in patients with metastatic ALK-positive NSCLC.
3.To assess the antitumor activity of ceritinib as measured by
ORR and DOR by Investigator assessment
TTR, DCR and PFS by BIRC and by Investigator assessment
in treatment-naive patients with metastatic ALK-positive NSCLC who have had ALK-positive status determined centrally by Ventana IHC following oral dosing of 450 mg or 600 mg ceritinib taken daily with a low-fat meal and 750 mg ceritinib taken daily in the fasted state.
4. To assess overall survival (OS) in treatment-naive patients with metastatic ALK-positive NSCLC who have had ALK-positive status determined centrally by Ventana IHC following oral dosing of 450 mg or 600 mg ceritinib taken daily with a low-fat meal and 750 mg ceritinib taken daily in the fasted state.
Inclution Criteria
Inclusion criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate
for definitive multimodality therapy) or IV ALK-positive NSCLC.
Eligible patients include those who are either previously treated with systemic anti-cancer
therapy for advanced disease, either experimental or not, or treatment-naive with the
exception of neo-adjuvant or adjuvant therapy (excluding regimens containing an ALK
inhibitor) as depicted in the inclusion criterion No. 13. (For AJCC stage groupings and
TNM definitions, refer to NCI 2014 guidelines).
For patients previously treated with systemic anti-cancer therapy (including crizotinib), ALK-positive status can be determined locally by using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). Locally confirmed results of ALKpositive status must be available prior to randomization. In instances where a local ALK-positive result is not available as described above, a central test to confirm ALK-positivity must be performed at a Novartis designated central laboratory using either archival tumor (obtained at or since the time of diagnosis) or a newly obtained tumor sample taken prior to randomization.
For patients who are treatment-naive, ALK-positivity must be determined prospectively at a Novartis central laboratory using the Ventana anti-ALK (D5F3) IHC test (Ventana IHC) prior to randomization. The Ventana IHC test must be performed on a biopsy obtained prior to randomization or on archival tumor obtained at or since the time of initial diagnosis.
Note: Patients with clinically and neurologically stable central nervous system (CNS)
metastases who have not required increasing doses of steroids within the 2 weeks prior to
study entry to manage CNS symptoms are eligible.
2. Age 18 years or older at the time of informed consen
3. Patients who are previously treated may have received one prior treatment regimen with
crizotinib (all other ALK inhibitors are excluded).
‧Patients previously treated with crizotinib must have discontinued treatment with
crizotinib at least 1 week (7 days) prior to the first dose of study drug.
4. Patients who are previously treated may have received prior chemotherapy, biologic
therapy, or other investigational agents. ALK inhibitors other than crizotinib are excluded.
Patients who have been treated with chemotherapy, biological therapy, or other
investigational agents must have discontinued the treatment at least 2 weeks (14 days)
prior to starting study drug. In case last chemotherapy contains nitroso-urea or
mitomycin C, the treatment must be discontinued at least 6 weeks prior to the first
dose of study drug.
5. Patients who have received prior chemotherapy, crizotinib, biologic therapy, or other
investigational agents must have recovered from all toxicities related to prior anticancer
therapies to grade ≤1 (CTCAE v 4. 03) prior to starting study drug. Patients with grade ≤2
peripheral neuropathy or any grade of alopecia, nail changes, or skin changes are allowed
to enter the study.
6. 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) ≤3.0 x ULN, except for patients with liver metastasis, who are only included if AST ≤5.0 x ULN
Alanine transaminase (ALT) ≤3.0 x ULN, except for patients with liver metastasis, who are only included if ALT ≤5.0 x ULN
Alkaline phosphatase (ALP) ≤5.0 x ULN
Serum amylase ≤ 2.0 xULN
Serum lipase ≤ ULN
Fasting plasma glucose ≤175 mg/dL (≤9.8 mmol/L)
7. Patient must have the following laboratory values within normal limits or corrected to
within normal limits with supplements before the first dose with ceritinib:
Potassium
Magnesium
Phosphorus
Total calcium (corrected for serum albumin)
8.Patient has a World Health Organization (WHO) performance status 0-2
9.Patient has the ability to understand and provide signed informed consent.
10.. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests
and other study procedure.
11. Treatment-naive patients must have at least one measurable lesion as defined by RECIST v.1.1 and confirmed by BIRC prior to randomization. A previously irradiated site lesion may be counted as a target lesion only if there is clear sign of progression since the
irradiation.
12. Treatment-naive patients who received neo-adjuvant or adjuvant therapy (excluding
regimens containing an ALK inhibitor) will be eligible for enrollment only if relapse has
occurred more than 12 months from the end of the neo-adjuvant or adjuvant systemic
therapy.
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate
for definitive multimodality therapy) or IV ALK-positive NSCLC.
Eligible patients include those who are either previously treated with systemic anti-cancer
therapy for advanced disease, either experimental or not, or treatment-naive with the
exception of neo-adjuvant or adjuvant therapy (excluding regimens containing an ALK
inhibitor) as depicted in the inclusion criterion No. 13. (For AJCC stage groupings and
TNM definitions, refer to NCI 2014 guidelines).
For patients previously treated with systemic anti-cancer therapy (including crizotinib), ALK-positive status can be determined locally by using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). Locally confirmed results of ALKpositive status must be available prior to randomization. In instances where a local ALK-positive result is not available as described above, a central test to confirm ALK-positivity must be performed at a Novartis designated central laboratory using either archival tumor (obtained at or since the time of diagnosis) or a newly obtained tumor sample taken prior to randomization.
For patients who are treatment-naive, ALK-positivity must be determined prospectively at a Novartis central laboratory using the Ventana anti-ALK (D5F3) IHC test (Ventana IHC) prior to randomization. The Ventana IHC test must be performed on a biopsy obtained prior to randomization or on archival tumor obtained at or since the time of initial diagnosis.
Note: Patients with clinically and neurologically stable central nervous system (CNS)
metastases who have not required increasing doses of steroids within the 2 weeks prior to
study entry to manage CNS symptoms are eligible.
2. Age 18 years or older at the time of informed consen
3. Patients who are previously treated may have received one prior treatment regimen with
crizotinib (all other ALK inhibitors are excluded).
‧Patients previously treated with crizotinib must have discontinued treatment with
crizotinib at least 1 week (7 days) prior to the first dose of study drug.
4. Patients who are previously treated may have received prior chemotherapy, biologic
therapy, or other investigational agents. ALK inhibitors other than crizotinib are excluded.
Patients who have been treated with chemotherapy, biological therapy, or other
investigational agents must have discontinued the treatment at least 2 weeks (14 days)
prior to starting study drug. In case last chemotherapy contains nitroso-urea or
mitomycin C, the treatment must be discontinued at least 6 weeks prior to the first
dose of study drug.
5. Patients who have received prior chemotherapy, crizotinib, biologic therapy, or other
investigational agents must have recovered from all toxicities related to prior anticancer
therapies to grade ≤1 (CTCAE v 4. 03) prior to starting study drug. Patients with grade ≤2
peripheral neuropathy or any grade of alopecia, nail changes, or skin changes are allowed
to enter the study.
6. 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) ≤3.0 x ULN, except for patients with liver metastasis, who are only included if AST ≤5.0 x ULN
Alanine transaminase (ALT) ≤3.0 x ULN, except for patients with liver metastasis, who are only included if ALT ≤5.0 x ULN
Alkaline phosphatase (ALP) ≤5.0 x ULN
Serum amylase ≤ 2.0 xULN
Serum lipase ≤ ULN
Fasting plasma glucose ≤175 mg/dL (≤9.8 mmol/L)
7. Patient must have the following laboratory values within normal limits or corrected to
within normal limits with supplements before the first dose with ceritinib:
Potassium
Magnesium
Phosphorus
Total calcium (corrected for serum albumin)
8.Patient has a World Health Organization (WHO) performance status 0-2
9.Patient has the ability to understand and provide signed informed consent.
10.. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests
and other study procedure.
11. Treatment-naive patients must have at least one measurable lesion as defined by RECIST v.1.1 and confirmed by BIRC prior to randomization. A previously irradiated site lesion may be counted as a target lesion only if there is clear sign of progression since the
irradiation.
12. Treatment-naive patients who received neo-adjuvant or adjuvant therapy (excluding
regimens containing an ALK inhibitor) will be eligible for enrollment only if relapse has
occurred more than 12 months from the end of the neo-adjuvant or adjuvant systemic
therapy.
Exclusion Criteria
Patients eligible for this study must not meet any of the following criteria:
1. Prior treatment with an ALK inhibitor other than crizotinib.
2. Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline
cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
3. History of carcinomatous meningitis.
4. Presence or history of a malignant disease other than an ALK-positive advanced tumor
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.
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
starting study treatment is allowed.
6. 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 antihypertensive 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 (as mean of triplicate ECGs).
7. 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).
8. 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.
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 (see Appendix 2):
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 tumor-associated symptoms (non-CNS), dose
must have been stabilized (or decreasing) for at least 5 days before first dose of study
treatment.
13. Patient is receiving treatment with any enzyme-inducing anticonvulsant (see Appendix 2)
that cannot be discontinued at least 1 week before first dose of study treatment, and for the
duration of the study. Patients on non-enzyme-inducing anticonvulsants are eligible.
14. Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within
4 weeks prior to starting study treatment 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 these
procedures.
15. Patients who have had, or are expected to have, regular alcohol intake exceeding 1
drink/day on a daily basis within 3 days prior to the days of blood sample collection for
PK assessment (i.e., ≤3 days prior to days 1 and 22 ) (note: 1 drink = 5 ounces of wine, 12
ounces of beer, or 1 ounce of hard liquor).
16. Patients who have consumed, or are expected to consume, grapefruits, pomegranates, star fruits, seville orange or product containing the juice of each within 3 days prior to the days of blood sample collection for PK assessment (e.g., ≤3 days prior to days 1 and 22). Note: vitamin supplements are allowed.
17. Pregnant or nursing (lactating) women.
18. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective contraception during the study
and for 3 months after stopping ceritinib treatment.
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), total hysterectomy, or tubal ligation at least 6 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 sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
Use of oral, injected, or implanted hormonal methods of contraception or placement
of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormonal vaginal ring or transdermal hormone contraception.
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.
19. Sexually active males must use a condom during intercourse while taking ceritinib and for 3 months after stopping ceritinib treatment. Male patients should not father a child for 3
months after the last dose of ceritinib treatment. A condom is required to be used also by
vasectomized men in order to prevent delivery of the drug via seminal fluid.
20. Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
1. Prior treatment with an ALK inhibitor other than crizotinib.
2. Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline
cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
3. History of carcinomatous meningitis.
4. Presence or history of a malignant disease other than an ALK-positive advanced tumor
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.
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
starting study treatment is allowed.
6. 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 antihypertensive 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 (as mean of triplicate ECGs).
7. 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).
8. 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.
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 (see Appendix 2):
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 tumor-associated symptoms (non-CNS), dose
must have been stabilized (or decreasing) for at least 5 days before first dose of study
treatment.
13. Patient is receiving treatment with any enzyme-inducing anticonvulsant (see Appendix 2)
that cannot be discontinued at least 1 week before first dose of study treatment, and for the
duration of the study. Patients on non-enzyme-inducing anticonvulsants are eligible.
14. Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within
4 weeks prior to starting study treatment 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 these
procedures.
15. Patients who have had, or are expected to have, regular alcohol intake exceeding 1
drink/day on a daily basis within 3 days prior to the days of blood sample collection for
PK assessment (i.e., ≤3 days prior to days 1 and 22 ) (note: 1 drink = 5 ounces of wine, 12
ounces of beer, or 1 ounce of hard liquor).
16. Patients who have consumed, or are expected to consume, grapefruits, pomegranates, star fruits, seville orange or product containing the juice of each within 3 days prior to the days of blood sample collection for PK assessment (e.g., ≤3 days prior to days 1 and 22). Note: vitamin supplements are allowed.
17. Pregnant or nursing (lactating) women.
18. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective contraception during the study
and for 3 months after stopping ceritinib treatment.
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), total hysterectomy, or tubal ligation at least 6 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 sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
Use of oral, injected, or implanted hormonal methods of contraception or placement
of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormonal vaginal ring or transdermal hormone contraception.
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.
19. Sexually active males must use a condom during intercourse while taking ceritinib and for 3 months after stopping ceritinib treatment. Male patients should not father a child for 3
months after the last dose of ceritinib treatment. A condom is required to be used also by
vasectomized men in order to prevent delivery of the drug via seminal fluid.
20. Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
The Estimated Number of Participants
-
Taiwan
11 participants
-
Global
306 participants
