Phase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Patients With Previously Untreated Extensive Stage Small-cell Lung Cancer

July 26, 2017 updated by: Amgen

Phase 1b/2, Multicenter, Open-label Study of Carfilzomib, Carboplatin, and Etoposide in Subjects With Previously Untreated Extensive-stage Small-cell Lung Cancer

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
        • Juravinski Cancer Centre
  • Russian Federation
      • Arkhangelsk, Russian Federation
        • State Budgetary Healthcare Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"
      • Moscow, Russian Federation
        • Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center"
      • St. Petersburg, Russian Federation
        • State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University"
      • Yaroslavl, Russian Federation
        • State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"
    • Kursk
      • Kislino, Kursk, Russian Federation
        • Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
  • United States
    • Connecticut
      • New Haven, Connecticut, United States
        • Yale University, Yale Cancer Center
    • Florida
      • Gainesville, Florida, United States
        • UF Health Davis Cancer Pavilion and Shands Med Plaza
    • Indiana
      • Goshen, Indiana, United States
        • Goshen Center for Cancer Care
      • Lafayette, Indiana, United States
        • Horizon Oncology Research, Inc.
      • Muncie, Indiana, United States
        • Indiana University Health Ball Memorial Hospital
    • Kentucky
      • Lexington, Kentucky, United States
        • Baptist Health Lexington Clinical Research Center
    • Maryland
      • Frederick, Maryland, United States
        • Frederick Memorial Hospital
    • New Jersey
      • Hackensack, New Jersey, United States
        • John Theurer Cancer Center At Hackensack UMC
    • North Carolina
      • Charlotte, North Carolina, United States
        • Levine Cancer Institute
      • Winston-Salem, North Carolina, United States
        • Wake Forest Baptist Health
    • Texas
      • Houston, Texas, United States
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  1. 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
  2. Subjects with asymptomatic brain metastases or other central nervous system (CNS) disease at screening/diagnosis are eligible
  3. Males and females ≥ 18 years of age
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Key Exclusion Criteria:

  1. 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.
  2. 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
  3. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Carfilzomib Combination
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.
Drug: Carfilzomib
Administered by intravenous infusion.
Other Names:
  • PR-171
  • Kyprolis®
  • PR171
Drug: Carboplatin
Administered by intravenous infusion.
Drug: Etoposide
Administered by intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-limiting Toxicities
Time Frame: First 21-day Cycle

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.
First 21-day Cycle

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs)
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.

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.
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.
Overall Survival (OS) - Phase 2
Time Frame: 30 months
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.
30 months
Maximum Plasma Concentration - Phase 2
Time Frame: Cycle 1 Day 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.
Cycle 1 Day 2
Time of Maximum Plasma Concentration - Phase 2
Time Frame: Cycle 1 Day 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.
Cycle 1 Day 2
Area Under Plasma Concentration-Time Curve - Phase 2
Time Frame: Cycle 1 Day 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.
Cycle 1 Day 2

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

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.
From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.
Overall Response Rate
Time Frame: From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

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.
From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.
Duration of Response
Time Frame: From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

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.
From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 5, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 4, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 6, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 12, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 19, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CFZ004
  • 2013-002597-44 (EudraCT Number)
  • 20130399 (Other Identifier: Amgen Inc.)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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