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Study to Assess Safety and Tolerability of MLN8237, In Combination With Erlotinib to Treat Non-Small Cell Lung Cancer | Clinical Trials | Clareo Health

TERMINATEDPHASE1/PHASE2

Study to Assess Safety and Tolerability of MLN8237, In Combination With Erlotinib to Treat Non-Small Cell Lung Cancer

A Phase I/II Trial to Assess Safety and Tolerability of an Oral Aurora Kinase A Inhibitor, MLN8237, In Combination With Erlotinib In Patients With Recurrent or Metastatic Non-Small Cell Lung Cancer

NCT01471964•Fox Chase Cancer Center

View on ClinicalTrials.gov

Summary

This phase I/II trial studies the side effects and the best dose of MLN8237 when given together with erlotinib hydrochloride and to see how well it works in treating patients with recurrent locally advanced or metastatic non-small cell lung cancer (NSCLC). MLN8237 and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES: I. Safety and tolerability of the combination treatment. (Phase I) II. Maximum tolerated dose (MTD) of MLN8237 (alisertib) when given in combination with standard dose erlotinib (erlotinib hydrochloride). (Phase I) III. Progression free survival. (Phase II) SECONDARY OBJECTIVES: I. Pharmacokinetic (PK) parameters of erlotinib and MLN8237, including, but not limited to maximum concentration of drug (Cmax), time of occurrence for maximum drug concentration (Tmax), and area under the curve from time zero to the last measurable concentration(AUC0-t last). II. Overall response rate (ORR), duration of response (DOR), time to progression (TTP), and overall survival (OS). (Phase II) III. Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values. (Phase II) OUTLINE: This is a phase I, dose-escalation study of alisertib followed by a phase II study. Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 and erlotinib hydrochloride PO once daily (QD) on days 1-21. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients with cytologically or histologically confirmed recurrent locally advanced or metastatic NSCLC have received at least one prior recognized systemic therapy for therapy for advanced disease, (recognized therapy must include a platinum doublet unless contraindicated due to organ dysfunction)
•Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
•Measurable disease by Response Evaluation Criteria in Solid Tumors- (RECIST) 1.1 criteria; previous irradiated tumor is acceptable if there is at least a 20% increase in the size of the previously irradiated lesion
•Absolute neutrophil count (ANC) \>= 1500/mm\^3
•Platelets \>= 100,000/mm\^3
•Hemoglobin (Hgb) \>= 9g/dL
•Total bilirubin =\< upper limit of normal (ULN)
•Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 1.5 x ULN; AST and/or ALT may be up to 5 X ULN if with known liver mets
•Adequate renal function as defined by: calculated creatinine clearance must be at least 40 mL/minute (Cockcroft-Gault)
•Serious, active infections must be controlled; patients may be enrolled while still on antibiotics as long as clinical signs of active infection are absent
+5 more criteria

Exclusion Criteria

•Prior treatment with an investigational or marketed inhibitor of the epidermal growth factor receptor (EGFR) pathway or an Aurora Kinase inhibitor
•Patients with mutations in the EGFR gene; the mutational status of all patients will be determined prior to study entry
•Prior malignancy within the past 3 years other than complete resection of basal or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy
•Prior systemic therapy within 14 days of initiating protocol treatment
•Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%; (ongoing small field radiation therapy for palliation only is allowed)
•Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study; anticonvulsants at stable doses are allowed
•Treatment with Proton Pump Inhibitor (PPI); patients on PPI therapy prior to enrollment must stop using the PPI for at least 4 days prior to the first dose of MLN8237
•Known central nervous system (CNS) disease, except for treated brain metastasis; treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) during the screening period; anticonvulsants (stable doses) are allowed; treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator \[LINAC\], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed \< 4 weeks prior to Day 1 will be excluded
•Uncontrolled or unstable medical or psychiatric co-morbidities which would clearly preclude use of MLN8237 or erlotinib
•Current, recent (within 2 weeks of enrollment of this study), or planned participation in an experimental drug study
+12 more criteria

Locations (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Key Dates

Start Date

October 20, 2011

Primary Completion Date

February 7, 2017

Completion Date

April 10, 2018

Last Updated

May 17, 2018

Enrollment

ACTUAL participants

Conditions

Non-small Cell Lung Cancer MetastaticNon-small Cell Lung Cancer Recurrent

Interventions

MLN8237 and Erlotinib

DRUG

Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

NCT07250477

Non-small Cell Lung Cancer Stage IIICNon-small Cell Lung Cancer Stage IV+3 more

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RECRUITINGPHASE2

Befotertinib and Icotinib for NSCLC With Uncommon EGFR Mutations

NCT06517953

Non-small Cell Lung Cancer MetastaticEGFR G719X+2 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 17, 2018Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Study to Assess Safety and Tolerability of MLN8237, In Combination With Erlotinib to Treat Non-Small Cell Lung Cancer

Inclusion Criteria

Exclusion Criteria

Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

Befotertinib and Icotinib for NSCLC With Uncommon EGFR Mutations

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