A clinical study evaluating ceritinib in tumors with ALK genetic abnormalities

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 106

Inclusion Criteria

- Written informed consent for the main study obtained prior to any screening procedure.
- Patient must have a histologically or cytologically confirmed diagnosis of one of the tumors that is ALK positive (ALK+). The ALK test results must be available at the investigator site before the first dose of the study drug. The tumor types are described below:
Anaplastic Large Cell Lymphoma (ALCL), local confirmation of diagnosis of ALK+ ALCL is sufficient for eligibility. Inflammatory Myofibroblastic Tumor locally documented translocation involving the ALK gene, Glioblastoma, Inflammatory breast cancer Any other locally documented ALK+ tumor. Must carry a locally documented genetic alteration of ALK including any of the following (ALK overexpression is also acceptable in Gliobalstoma):
- A known activating mutation in the kinase domain of ALK or a point mutation in the kinase domain of ALK that results in an amino acid change that has not been reported in normal germline DNA, or any other mutation (e.g. insertion or deletion) which results in a change in the amino acid sequence of the kinase domain of ALK, as long as the alteration does not clearly result in inactivation of the kinase activity, such as deletion of the kinase domain, or a stop codon preventing translation of the kinase domain.
- An amplification of the ALK gene, defined as = 6 copies per cell, or 3 copies per haploid genome. When assessed by FISH, ALK amplification must be observed in focal clusters of tumor cells (not only single cells) or in more than one-third of the tumor cells.
- A translocation involving the ALK gene.
- Glioblastoma patients only, overexpression of ALK protein documented locally is also acceptable for eligibility.
- Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for potential retrospective ALK testing at a Novartis designated central laboratory by a comparative technology: the confirmation of ALK positivity is not required for enrollment if other inclusion and exclusion criteria are fulfilled
- Patient is 18 years or older at the time of informed consent.
- Patient has WHO performance status = 2.
- Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation

Other protocol related inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

1. Patient with ALK+ lung cancer.
2. Patient with known hypersensitivity to any of the excipients of LDK378.
3. Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
4. History of carcinomatous meningitis.
5. Patient with diarrhea CTCAE = grade 2; or patients with neuropathy CTCAE = grade 2

Other protocol related exclusion criteria may apply.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the antitumor activity of ceritinib as measured by DCR determined by investigators;Secondary Objective: - To assess the antitumor activity of ceritinib as measured by ORR, DOR, TTR as determined by investigators<br>- To assess the antitumor activity of ceritinib as measured by PFS determined by investigators<br>- To assess the safety and tolerability of ceritinib. ;Primary end point(s): DCR, defined as the proportion of patients with best overall response of CR, PR, or SD = 16 weeks;Timepoint(s) of evaluation of this end point: at week 16

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. ORR, defined as the proportion of patients with a best overall response defined as CR or PR; (CR+PR)<br>2. The following endpoints will be evaluated by investigator assessment :<br>– DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause<br>- TTR, defined as the time from date of the first dose to date of first documented response (CR or PR) <br>– PFS, defined as time from date of the first dose to date of first documented disease progression or date of death due to any cause<br>3. ECG, Performance status, Vital signs, Physical examination; AEs, and laboratory (hematology, biochemistry, urinalysis, coagulation, pregnancy test and hormones (males only)<br>;Timepoint(s) of evaluation of this end point: at week 16

Updated 4/29/2024

A clinical study evaluating ceritinib in tumors with ALK genetic abnormalities

Recruitment & Eligibility

Study & Design

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