Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT02321501|
Recruitment Status : Recruiting
First Posted : December 22, 2014
Last Update Posted : September 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|ALK Positive Locally Advanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm ROS1 Gene Rearrangement Stage IIIB Lung Non-Small Cell Cancer AJCC v7 Stage IV Lung Non-Small Cell Cancer AJCC v7||Drug: Ceritinib Drug: Everolimus Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
I. To determine the maximum tolerated dose (MTD) of ceritinib (novel, potent and selective small molecule anaplastic lymphoma kinase [ALK] inhibitor) in combination with everolimus (a mammalian target of rapamycin [mTOR] inhibitor) in advanced cancers.
I. Preliminary descriptive assessment of the anti-tumor activity (response rate) of the combination in advanced non-small cell lung cancer (NSCLC) based upon Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
II. To determine the pharmacokinetics of ceritinib and everolimus used in combination.
III. To determine the safety of ceritinib and everolimus used in combination. IV. To evaluate the toxicities and tolerability of the combinations. V. To document anti-tumor activity (disease control rate at 8 weeks and progression-free survival).
I. To explore baseline molecular markers that may predict clinical activity, and to explore pharmacodynamic markers in blood, tumor tissue and molecular imaging that may predict an increase in apoptosis and clinical activity.
II. To determine concordance of ALK (protein levels on immunohistochemistry, fusion detection by fluorescence in situ hybridization [FISH] and somatic mutations).
III. To determine ribosomal protein S6 kinase (S6K) phosphorylation as a measure of mTOR inhibition.
OUTLINE: This is a dose-escalation study.
Patients receive ceritinib orally (PO) once daily (QD) and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/Ib Dose Escalation and Biomarker Study of Ceritinib (LDK378) in Combination With Everolimus in Patients With Locally Advanced or Metastatic Solid Tumors With an Expansion in NSCLC Characterized by Abnormalities in Anaplastic Lymphoma Kinase (ALK) Expression|
|Actual Study Start Date :||June 22, 2016|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2023|
Experimental: Treatment (ceritinib, everolimus)
Patients receive ceritinib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose (MTD) of ceritinib and everolimus, defined as the highest dose level in which 6 patients were treated with at most 1 experiencing a dose limiting toxicity [ Time Frame: 28 days ]MTD will be assessed.
- Response rate [ Time Frame: Up to 28 days after discontinuation of study drugs ]Evaluated based upon Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Progression-free survival [ Time Frame: Time from the start of the study until disease progressive or death, assessed up to 28 days after discontinuation of study drugs ]Progression free survival will be analyzed.
- Pharmacokinetic parameters of everolimus and ceritinib [ Time Frame: Days 1, 15, and 21 (course 1), day 1 (course 2), day 1 (course 3), and at progression ]Estimated and calculated using a noncompartmental pharmacokinetic model. Plasma concentrations and pharmacokinetic parameters for each drug dose will be summarized using descriptive statistics and the mean plasma concentrations for each drug dose will be plotted versus time.
- Levels of biomarkers as measured by immunohistochemistry, multiplex technology and/or enzyme-linked immunosorbent assays [ Time Frame: Up to 28 days after discontinuation of study drugs ]The specific arm is to evaluate whether biomarkers can be correlated with clinical benefit or used as potential markers of biological activity, therapeutic sensitivity, or resistance.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02321501
|Contact: George Blumenscheinfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: George R. Blumenschein 713-792-6363|
|Principal Investigator: George R. Blumenschein|
|Principal Investigator:||George R Blumenschein||M.D. Anderson Cancer Center|