Primary objective: Estimate the MTD and/or RDE of LDK378 as a single agent when administered orally to pediatric patients with ALK-activated tumors in the fasted and in fed stateSecondary objectives: Objective 1: Characterize the safety and…
ID
Source
Brief title
Condition
- Other condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Health condition
Alle maliginiteiten met een ALK mutatie.
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: Incidence rate of Dose Limiting Toxicities (DLT) during the
first cycle of LDK378 treatment.
Secondary outcome
Secondary endpoints:
Endpoint 1: Adverse events and serious adverse events, changes in laboratory
values, assessments of physical examinations, vital signs and
electrocardiograms.
Endpoint 2: Plasma concentration time profiles, PK parameters, including but
not limited to AUClast, AUCtau, Cmin, Cmax, Tmax, Racc, and T1/2,acc
Endpoint 3: Overall response rate (ORR) and duration of response (DOR),
progression-free survival (PFS) as per RECIST 1.1 in patients with
neuroblastoma and other solid tumors, and by International Working Group (IWG)
criteria in patients with lymphoma. MIBG response in patients with
neuroblastoma. Resolution of bone marrow disease in patients with
neuroblastoma.
Background summary
LDK378 is a novel inhibitor of ALK that is active in a broad range of
ALKactivated tumor models, including models driven by mutated versions of
ALK known to be resistant to crizotinib, and by ALK gene amplification. The
primary purpose of this study is to determine the maximum tolerated
dose (MTD) and/or recommended dose for expansion (RDE) in pediatric patients in
the fasted and in fed state, and to delineate a clinical dose to be used in any
future pediatric
studies. This study will also assess the safety, tolerability, PK and
preliminary evidence of antitumor activity of LDK378 in pediatric patients
with neuroblastoma, and other ALK-activated tumors.
Study objective
Primary objective: Estimate the MTD and/or RDE of LDK378 as a single agent when
administered orally to pediatric patients with ALK-activated tumors in the
fasted and in fed state
Secondary objectives:
Objective 1: Characterize the safety and tolerability of LDK378 in pediatric
patients in the fasted and in fed state
Objective 2: Characterize single and multiple-dose PK of LDK378 in pediatric
patients in the fasted and in fed state
Objective 3: Assess the anti-tumor activity of LDK378 in the fasted and in fed
state
Study design
This is a two-part, phase 1 study, with a dose escalation part followed by an
expansion part. The expansion part will start after the MTD/RDE has
been determined. The expansion part will include 2 groups of patients, one
restricted to patients with ALK-activated neuroblastoma in the fasted and in
fed state and the second including patients with all other ALK-activated
tumors. Enrollment will proceed in parallel. LDK378 will be administered
orally, once daily, continuously.
Intervention
Children will be treated with oral LDK378 long as they will benefit from it.
Response assessment every 21 days.
Study burden and risks
Risk:
Side effects of the study medication (see also the dose-limiting toxicities
described on page 35, Table 6-2), drawing blood samples and tissue biopsies.
Het collection of blood can cause a bruise, bleeding at the site or blood
clothing. These usually disappear naturally.
Burden:
-study visits 2 times per 21 days for 2 years after proceeding though the
screening.
-blood draws for lab tests every visit
-other assesments such as tissue biospies, ECGs and radiology tests.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
- Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists ;- Age * 12 months and <18 years ;- The tumor must carry a genetic alteration of ALK ;- Patients must have evaluable or measurable disease;Other protocol-defined inclusion criteria may apply
Exclusion criteria
- Symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease ;- Clinically significant, uncontrolled heart disease ;- Inadequate end organ function as defined by specified laboratory values;- History of known of interstitial lung disease or interstitial pneumonitis, including
clinically significant radiation pneumonitis (i.e., affecting activities of daily living or
requiring therapeutic intervention).;-Radiotherapy to lungs * 4 weeks prior to starting the study treatment or
patients who have not recovered from radiotherapy related toxicities. For
all other anatomic sites, radiotherapy * 2 weeks prior to starting the study treatment.;- Use of medications that are known to be strong inhibitors or inducers of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study ;- Use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study.;- Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.;Other protocol-defined exclusion criteria may apply
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002074-31-NL |
| CCMO | NL43465.078.13 |