Study of Everolimus, Pemetrexed, Carboplatin, and Bevacizumab to Treat Stage IV Lung Cancer
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.
Non Small Cell Lung Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Dose Escalation Study of Everolimus, Pemetrexed, Carboplatin, and Bevacizumab in Stage IV Non-Squamous Non-Small Cell Lung Cancer|
- 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. [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
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.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
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
- Antitumor efficacy associated with administration of everolimus/pemetrexed/carboplatin/bevacizumab administration in patients with Stage IV non-squamous NSCLC. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]number of patients with a response according to the Response Evaluation Criteria in Solid Tumors (RECIST)
- Progression-free survival (PFS) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]time from start of treatment to time of progression or death (overall PFS)
- Overall Survival (OS) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]measured from the start of treatment to time of death.
|Study Start Date:||September 2012|
|Study Completion Date:||October 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Experimental Phase I Dose Escalation
Pemetrexed: intravenous; 500 mg/m² for Dose Levels 1, 2 and 3
Carboplatin: intravenous; 5 AUC for Dose Level 1; 6 AUC for Dose Levels 2 and 3
Bevacizumab: intravenous; 15 mg/kg for Dose Levels 1, 2, and 3
Everolimus: oral, 2.5 mg/day for Dose Levels 1 and 2; 5.0 mg/day for Dose Level 3
Other Names:Drug: Pemetrexed
Other Name: AlimtaDrug: Carboplatin
Other Names:Drug: Bevacizumab
Other Name: Avastin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700400
|United States, Arizona|
|University of Arizona Cancer Center|
|Tuscon, Arizona, United States, 85724|
|United States, Kentucky|
|University of Kentucky Markey Cancer Center|
|Lexington, Kentucky, United States, 40536|
|United States, Oregon|
|Providence Cancer Center|
|Portland, Oregon, United States, 97213|
|United States, Washington|
|Cancer Research And Biostatistics Clinical Trials Consortium|
|Seattle, Washington, United States, 98101|
|Principal Investigator:||Linda L. Garland, MD||University of Arizona|
|Study Chair:||John Crowley, PhD||Cancer Research And Bioststistics|