A clinical research study to find out if the drug LDK378 is safe and has beneficial effects in people who have a particular type of lung cancer called â??ALK positiveâ?? non-small cell lung cancer.
- Conditions
- Health Condition 1: null- Previously untreated ALK-positive, non-squamous non-small cell lung cancer
- Registration Number
- CTRI/2014/07/004753
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous NSCLC
that is ALK positive as assessed by the Ventana IHC test. The test will be performed at
Novartis designated central laboratories
2. Patient has newly diagnosed stage IIIB or IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy as depicted in criterion 6. (For AJCC stage groupings and TNM definitions, refer to NCI 2012 guidelines)
3. Patient has at least one 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 with clinically and neurologically stable central nervous system metastases
who have not required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms
5. Patient is 18 years of age or older at the time of informed consent.
6. Patient who received previous neo-adjuvant or adjuvant systemic therapy will be eligible
for enrollment only if relapse has occurred more than 12 months from the end of the neoadjuvant
or adjuvant systemic therapy. Patients must have recovered from all toxicities related to prior (neo-) adjuvant systemic therapy to grade less than or eual to 1 (CTCAE v 4.03). Exception
to this criterion: patients with any grade of alopecia are allowed to enter the study.
7. Patient must meet the following laboratory values at the screening visit:
• WBC count greater than or equal to 4 x 10 raised to 9 per L
• Absolute Neutrophil Count greater than or equal to 1.5 x 10 raised to 9 per L
• Platelets greater than or equal to 100 x 10 raised to 9 per L
• Hemoglobin (Hgb) greater than or equal to 9 g per dL
• Serum creatinine less than 1.5 mg per dL and /or calculated creatinine clearance (using
Cockcroft-Gault formula) greater than or equal to 50 mL per min
• Total bilirubin less than 1.5 x ULN except for patients with Gilbertâ??s syndrome who may
only be included if total bilirubin less than 3 x ULN or direct bilirubin less than 1.5 x ULN
• Aspartate transaminase (AST) less than 2.5 x ULN, except for patients with liver metastasis,
who are only included if AST less than 5 x ULN
• Alanine transaminase (ALT) less than 2.5 x ULN, except for patients with liver metastasis,
who are only included if ALT less than 5 x ULN
• Alkaline phosphatase (ALP) less than 5 x ULN
8. Patient must have the following laboratory values greater than or equal to lower limit of normal (LLN) or corrected to within normal limits with supplements during screening:
• Potassium greater than or equal to LLN
• Magnesium greater than or equal to LLN
• Phosphorus greater than or equal to LLN
• Total calcium (corrected for serum albumin) greater than or equal to LLN
9. Patient has life expectancy greater than or equal to 12 weeks.
10. Patient has a WHO performance status 0-2.
11. Patient has the ability to understand and provide signed informed consent.
1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline
cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
2. Patient with a history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs.
3. Patient has received previous systemic anticancer therapy (e.g. cytotoxic drugs,
monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted
therapies, either experimental or not) for newly diagnosed stage IIIB or IV NSCLC or
relapsed locally advanced or metastatic NSCLC with exception of neo-adjuvant or
adjuvant therapy as depicted in inclusion criteria 6.
4. Patient with symptomatic CNS metastases who is neurologically unstable or has required
increasing doses of steroids within the 2 weeks prior to screening to manage CNS
symptoms.
5. Patient has history of carcinomatous meningitis.
6. Patient has received radiotherapy less than or equal to 2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions less than or equal to 2 weeks prior to starting study treatment is allowed.
7. Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within
4 weeks prior (2 weeks for resection of brain metastases) 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 greater than or equal to 1 week after the procedure.
8. 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.
9. 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) greater than or equal to 160 mm Hg and/or Diastolic Blood Pressure (DBP) greater than or equal to 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) greater than 470 ms using Fridericiaâ??s correction on the screening ECG
(as mean of triplicate ECGs)
10. Patient has impairment of GI function or GI disease that may significantly alter the
absorption of LDK378 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
or malabsorption syndrome).
11. Patient receiving treatment with medications that meet one of the following criteria and
that cannot be d
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method