Back to resultsPhase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Patients With Previously Untreated Extensive Stage Small-cell Lung Cancer
Primary Purpose
Extensive-Stage Small-Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Carfilzomib
Carboplatin
Etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Extensive-Stage Small-Cell Lung Cancer
Eligibility Criteria
Key Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of extensive-stage small-cell lung cancer (ES-SCLC) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; ES-SCLC is defined as: small-cell lung cancer (SCLC) that has spread beyond one hemithorax and regional lymph nodes on the same side (e.g., supraclavicular) to the contralateral hemithorax, lymph nodes, or more distant locations in the body
- Subjects with asymptomatic brain metastases or other central nervous system (CNS) disease at screening/diagnosis are eligible
- Males and females ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Key Exclusion Criteria:
- Previous systemic therapy to treat small-cell lung cancer (SCLC). Subjects with recurrent or progressive limited-stage SCLC after previous systemic treatment are not eligible for study participation.
- Whole brain or focal radiation therapy within 14 days prior to Cycle 1 Day 1 (C1D1) for Phase 1b or prior to randomization for Phase 2
- Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to prior to C1D1 for Phase 1b or prior to randomization for Phase 2
Sites / Locations
- Yale University, Yale Cancer Center
- UF Health Davis Cancer Pavilion and Shands Med Plaza
- Goshen Center for Cancer Care
- Horizon Oncology Research, Inc.
- Indiana University Health Ball Memorial Hospital
- Baptist Health Lexington Clinical Research Center
- Frederick Memorial Hospital
- John Theurer Cancer Center at Hackensack UMC
- Levine Cancer Institute
- Wake Forest Baptist Health
- The University of Texas MD Anderson Cancer Center
- Juravinski Cancer Centre
- Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
- State budgetary healthcare institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"
- Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center"
- State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University"
- State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Carfilzomib Combination
Arm Description
Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle as per the dose escalation schema, carboplatin at a target area under the curve (AUC) of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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 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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01987232
Brief Title
Phase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Patients With Previously Untreated Extensive Stage Small-cell Lung Cancer
Official Title
Phase 1b/2, Multicenter, Open-label Study of Carfilzomib, Carboplatin, and Etoposide in Subjects With Previously Untreated Extensive-stage Small-cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
November 5, 2013 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
May 4, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extensive-Stage Small-Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carfilzomib Combination
Arm Type
Experimental
Arm Description
Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle as per the dose escalation schema, carboplatin at a target area under the curve (AUC) of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
PR-171, PR171, Kyprolis®
Intervention Description
Administered by intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Administered by intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
Administered by intravenous infusion.
Primary Outcome Measure Information:
Title
Number of Participants With Dose-limiting Toxicities
Description
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
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Title
Overall Survival (OS) - Phase 2
Description
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
Title
Maximum Plasma Concentration - Phase 2
Description
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
Title
Time of Maximum Plasma Concentration - Phase 2
Description
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
Title
Area Under Plasma Concentration-Time Curve - Phase 2
Description
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
Other Pre-specified Outcome Measures:
Title
Progression-free Survival
Description
Progression-free survival (PFS) was specified as a primary endpoint for the phase 2 portion of the study. Since phase 2 did not proceed PFS was analyzed in phase 1b participants on an exploratory basis. PFS was defined as the time from the start of treatment to documented disease progression or death due to any cause, whichever occurred first. Disease progression was determined by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, defined as at least a 20% increase in the size of target lesions (absolute increase ≥ 5 mm), unequivocal progression of existing non-target lesions, or any new lesions.
Median PFS was calculated using Kaplan-Meier methods. Participants with no baseline disease assessments, who started a new anticancer therapy before documentation of PD or death, with death or PD immediately after more than 1 consecutively missed disease assessment visit or alive without documentation of PD before the data cutoff date were censored.
Time Frame
From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.
Title
Overall Response Rate
Description
The overall response rate (ORR) was defined as the percentage of participants for whom the best overall confirmed response was either complete response (CR) or partial response (PR) assessed by the investigator according to RECIST v1.1 criteria.
CR: Disappearance of all target and non-target lesions, no new lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters, or, the disappearance of all target lesions and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits.
Time Frame
From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.
Title
Duration of Response
Description
Duration of response (DOR) was calculated for participants who achieved a confirmed CR or PR. defined as the time from first evidence of confirmed PR/CR to disease progression or death due to any cause. Median DOR was calculated using Kaplan-Meier methods. Participants with no baseline disease assessments, who started a new anticancer therapy before documentation of PD or death, with death or PD immediately after more than 1 consecutively missed disease assessment visit or alive without documentation of PD before the data cutoff date were censored.
DOR was originally specified as a secondary endpoint for the phase 2 portion of the study. Since phase 2 did not proceed, DOR was analyzed in phase 1b participants on an exploratory basis.
Time Frame
From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of extensive-stage small-cell lung cancer (ES-SCLC) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; ES-SCLC is defined as: small-cell lung cancer (SCLC) that has spread beyond one hemithorax and regional lymph nodes on the same side (e.g., supraclavicular) to the contralateral hemithorax, lymph nodes, or more distant locations in the body
Subjects with asymptomatic brain metastases or other central nervous system (CNS) disease at screening/diagnosis are eligible
Males and females ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Key Exclusion Criteria:
Previous systemic therapy to treat small-cell lung cancer (SCLC). Subjects with recurrent or progressive limited-stage SCLC after previous systemic treatment are not eligible for study participation.
Whole brain or focal radiation therapy within 14 days prior to Cycle 1 Day 1 (C1D1) for Phase 1b or prior to randomization for Phase 2
Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to prior to C1D1 for Phase 1b or prior to randomization for Phase 2
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Yale University, Yale Cancer Center
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
UF Health Davis Cancer Pavilion and Shands Med Plaza
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
Goshen Center for Cancer Care
City
Goshen
State/Province
Indiana
Country
United States
Facility Name
Horizon Oncology Research, Inc.
City
Lafayette
State/Province
Indiana
Country
United States
Facility Name
Indiana University Health Ball Memorial Hospital
City
Muncie
State/Province
Indiana
Country
United States
Facility Name
Baptist Health Lexington Clinical Research Center
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
Frederick Memorial Hospital
City
Frederick
State/Province
Maryland
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack UMC
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
Country
United States
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
City
Kislino
State/Province
Kursk
Country
Russian Federation
Facility Name
State budgetary healthcare institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"
City
Arkhangelsk
Country
Russian Federation
Facility Name
Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center"
City
Moscow
Country
Russian Federation
Facility Name
State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University"
City
St. Petersburg
Country
Russian Federation
Facility Name
State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"
City
Yaroslavl
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
Phase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Patients With Previously Untreated Extensive Stage Small-cell Lung Cancer
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