Expanded treatment protocol to find out if the drug LDK378 is safe in people who have a particular type of lung cancer called â??ALK positiveâ?? non-small cell lung cancer

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2014/12/005250
• Date of registration: 04-12-2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Healthcare Private Limited
• Public title: Expanded treatment protocol to find out if the drug LDK378 is safe in people who have a particular type of lung cancer called â??ALK positiveâ?? non-small cell lung cancer
• Scientific title: An open-label, multi-center, Expanded Treatment Protocol (ETP) of oral LDK378 in adult patients with non-small cell lung cancer (NSCLC) characterized by ALK positivity - Expanded Treatment Protocol
• Date of first enrolment: 31-12-2014
• Target sample size: 2600
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=9429
• Study type: Interventional
• Study design: Single Arm Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 3/ Phase 4

Countries of recruitment

India, Malaysia, Thailand, United States of America

Contacts

• Name: Dr Manish Mistry
• Affiliation: Medical Director

• Name: Dr Manish Mistry
• Affiliation: Medical Director

Key inclusion & exclusion criteria

Inclusion criteria: Histologically or cytologically confirmed diagnosis of NSCLC that demonstrates ALK positivity as assessed by approved FISH test (Abbott Molecular Inc), using Vysis break apart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test. If documentation of ALK positivity is not available, the test to confirm ALK positivity must be performed according to the above criterion, using a new tumor biopsy obtained prior to the first dose of ETP treatment (LDK378).

Stage IIIB or IV NSCLC patient with documented disease progression at enrollment, and who does not qualify or have access to LDK378 through a clinical trial.

Patients who have been pre-treated with an ALK inhibitor for locally advanced or metastatic NSCLC.

Patient is 18 years of age or older at the time of informed consent

Life expectancy >= 12 weeks

WHO performance status 0-3



Patients must have recovered from all toxicities related to prior anticancer therapies to <= grade 2 (CTCAE v 4.03),

The following laboratory criteria have been met:

Absolute neutrophil count (ANC) >= 1.5 x 109/L

Hemoglobin (Hgb) >= 8 g/dL

Platelets >= 75 x 109/L

Serum total bilirubin <= 1.5 x upper limit of normal (ULN), except for patients with

Gilbertâ??s syndrome who may be included if total bilirubin <= 3.0 x ULN and 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 x ULN; alanine transaminase (ALT) < 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT < 5 x ULN

Calculated or measured creatinine clearance (CrCL) >= 30 mL/min

Magnesium >= LLN

Phosphorus >= LLN

Total calcium (corrected for serum albumin) >= LLN


Exclusion criteria: Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to ETP entry to manage CNS symptoms

The patient is less than 5 half-lives from prior ALK inhibitor or targeted therapy (for adequate wash-out) without recovery from treatment toxicities to grade 1 or to their pretreatment levels.

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.



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 >=1 week after the procedure.

Patient with a concurrent malignancy or history of a malignant disease other than NSCLC 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 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

Corrected QT (QTcF) 470 ms using Fridericiaâ??s correction on the screening ECG (as mean of triplicate ECGs)

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).

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 LDK378 and for the duration of the study:

Strong inhibitors or strong inducers of CYP3A4/5

Medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes

Patient is currently receiving treatment with warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants.

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. Patient on non enzyme-inducing anticonvulsants is eligible.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- adult patients with non-small cell lung cancer (NSCLC) ALK positivity

Intervention(s)

Intervention1: LDK378: 750 mg QD, this therapy will go on it patient has disease progression or Unacceptable toxicity or withdraws concent.
Control Intervention1: NA: NA

Primary Outcome(s)

To evaluate safety of LDK378, when used

in patients with ALK Positive locally advanced

or metastatic NSCLCTimepoint: To evaluate safety of LDK378, when used

in patients with ALK Positive locally advanced

or metastatic NSCLC

Secondary Outcome(s)

To provide early treatment access with

LDK378 to patients with ALK positive locally

advanced or metastatic NSCLCTimepoint: Drug administration records

Secondary ID(s)

CLDK378A2402_Version 5.0 dated 13-Nov-2015

Source(s) of Monetary Support

Novartis Healthcare Private Limited, sandoz House, Shivsagar Estate, Worli, Mumbai - 400012

Ethics review

Status: Approved
Approval date: 21/08/2014
Contact:

Institutional Review Board RGCI