The purpose of this study is to determine whether the investigational study drug everolimus may be used to increase the effectiveness of chemotherapy treatment for patients with advanced lung cancer.
Advanced lung cancer remains an incurable disease although new agents and new treatment strategies have resulted in improved survival outcomes for patients. Most recently there has been interest in augmenting tumor response to chemotherapy by the addition of drugs which inhibit tumor cell growth and proliferation. Everolimus is a new cancer drug which works as an inhibitor of mammalian target of rapamycin (or mTOR), mTOR is a protein that is part of a signaling pathway which can cause cancer cells to divide. Everolimus when used alone as a single agent has produced some response as well as prolonged stable disease in both chemo-naïve and pre-treated non-small cell lung cancer. The goal of this study is to evaluate the safety of everolimus with combined other cancer drugs called pemetrexed, carboplatin, and bevacizumab. Pemetrexed and carboplatin are both chemotherapy drugs and bevacizumab inhibits the growth of new blood vessels. Patients will be entered onto dosing cohorts of 3 patients according to the following dose escalation scheme. The first cohort will begin at dose level 1. At least three patients on each dose level must have completed cycle one before the study leadership (principal investigators, study statisticians) will allow patients to be enrolled onto the successive dose level. Dose Levels: 1, 2, 3 Pemetrexed (mg/m²): 500, 500, 500 Carboplatin (AUC): 5, 6, 6 Bevacizumab (mg/kg): 15, 15, 15 Everolimus (mg/day): 2.5, 2.5, 5.0 The purpose of this study is to determine the maximum tolerated dose, or MTD, for the combination of everolimus with pemetrexed, carboplatin, and bevacizumab in patients with Stage IV non-squamous, non small cell lung cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
University of Arizona Cancer Center
Tuscon, Arizona, United States
University of Kentucky Markey Cancer Center
Lexington, Kentucky, United States
Providence Cancer Center
Portland, Oregon, United States
Cancer Research And Biostatistics Clinical Trials Consortium
Seattle, Washington, United States
Define the Maximum Tolerated Dose (MTD) and Recommended Phase Two Dose (RPTD) of the combination of everolimus with pemetrexed, carboplatin, and bevacizumab in patients with Stage IV non-squamous NSCLC.
Pemetrexed, carboplatin and bevacizumab will be given intravenously on day 1 of a 21-day cycle with doses determined by the dose level to which the patient is assigned. Everolimus will be taken orally days 1-21 of a 21-day cycle. There will be no rest between each 21 day cycle. Tumor scans will be done every 2 treatment cycles. Patients who are not progressing and who are tolerating therapy will be treated with 6 cycles of Pem/Carbo/Bev/Everolimus followed by maintenance Pem/Bev/Everolimus, which will be continued if there is no tumor progression and the patient is tolerating therapy. If there is toxicity related specifically to one of the maintenance drugs, that drug will be discontinued and the other drugs will be maintained.
Time frame: up to 2 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Dose Limiting Toxicity (DLT) adverse events related to everolimus/pemetrexed/carboplatin/bevacizumab administration in patients with Stage IV non-squamous NSCLC. DLTs will be defined during cycle 1 only. Grading of adverse events will be according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Hematologic Adverse Events are defined as: Grade 4 neutropenia lasting greater than 5 days; Grade 3 or 4 febrile neutropenia; and/or Grade 4 thrombocytopenia Non-hematologic Adverse Events are defined as: Grade 3 or greater non-hematologic excluding the following: Hypersensitivity reaction grade 3 or 4 occurring on day 1 or day 15; Nausea/vomiting grade 3 or 4 in the absence of optimal antiemetics; Diarrhea grade 3 or 4 in the absence of optimal anti-diarrheal therapy; Asthenia grade 3 or 4 of less than 2 weeks duration; and/or Hyperglycemia grade 3 or 4 temporally related to corticosteroid pre-or post-medication
Time frame: up to 2 years
Antitumor efficacy associated with administration of everolimus/pemetrexed/carboplatin/bevacizumab administration in patients with Stage IV non-squamous NSCLC.
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number of patients with a response according to the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: up to 2 years
Progression-free survival (PFS)
time from start of treatment to time of progression or death (overall PFS)
Time frame: up to 2 years
Overall Survival (OS)
measured from the start of treatment to time of death.
Time frame: up to 2 years