The purpose of this study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of carfilzomib given in combination with carboplatin and etoposide as initial therapy for patients with extensive-stage small-cell lung cancer (ES SCLC).
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Administered by intravenous infusion.
Administered by intravenous infusion.
Administered by intravenous infusion.
Yale University, Yale Cancer Center
New Haven, Connecticut, United States
UF Health Davis Cancer Pavilion and Shands Med Plaza
Number of Participants With Dose-limiting Toxicities
The maximum tolerated dose (MTD) was defined as the highest dose level at which \< 33% of participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle. Dose-limiting toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. A DLT was defined as: * A grade 3 or greater non-hematologic toxicity that was assessed as related to carfilzomib by the investigator except in the case of neuropathy. A grade 2 or higher neuropathy with pain was considered a DLT. * Grade 4 neutropenia: absolute neutrophil count (ANC) \< 500 mm³, lasting ≥ 7 days despite granulocyte colony stimulating factor support, or any febrile (temperature \> 38.3°C) neutropenia (ANC \< 1000 mm³). * Thrombocytopenia of any grade associated with clinically significant bleeding or platelet/blood transfusion * Grade 4 fatigue lasting ≥ 7 days * Grade 3 nausea, vomiting or diarrhea lasting ≥ 7 days.
Time frame: First 21-day Cycle
Number of Participants With Adverse Events (AEs)
The severity of each adverse event was assessed using the NCI-CTCAE Version 4.03 according to the following: Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL Grade 4 - Life-threatening Grade 5 - Fatal. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
Time frame: From first day of any study treatment (i.e., carfilzomib, carboplatin, or etoposide) up to 30 days after the last day of study treatment. The median overall duration of treatment was 16 weeks.
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Gainesville, Florida, United States
Goshen Center for Cancer Care
Goshen, Indiana, United States
Horizon Oncology Research, Inc.
Lafayette, Indiana, United States
Indiana University Health Ball Memorial Hospital
Muncie, Indiana, United States
Baptist Health Lexington Clinical Research Center
Lexington, Kentucky, United States
Frederick Memorial Hospital
Frederick, Maryland, United States
John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
...and 7 more locations
Overall Survival (OS) - Phase 2
Overall Survival (OS) is defined as the time from randomization to the date of death. Overall survival was a specified secondary endpoint for the phase 2 portion of the study; since phase 2was not conducted, OS was not analyzed.
Time frame: 30 months
Maximum Plasma Concentration - Phase 2
Pharmacokinetic (PK) analyses were specified as secondary endpoints for the phase 2 portion of the study; since phase 2 was not conducted, PK analyses were not performed.
Time frame: Cycle 1 Day 2
Time of Maximum Plasma Concentration - Phase 2
Pharmacokinetic (PK) analyses were specified as secondary endpoints for the phase 2 portion of the study; since phase 2 was not conducted, PK analyses were not performed.
Time frame: Cycle 1 Day 2
Area Under Plasma Concentration-Time Curve - Phase 2
Pharmacokinetic (PK) analyses were specified as secondary endpoints for the phase 2 portion of the study; since phase 2 was not conducted, PK analyses were not performed.
Time frame: Cycle 1 Day 2