Extensive-Stage Small-Cell Lung CancerPhase 1/2NCT01987232
Phase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Patients With Previously Untreated Extensive Stage Small-cell Lung Cancer
A Phase 1/2 study testing Carfilzomib, Carboplatin and Etoposide in people with Extensive-Stage Small-Cell Lung Cancer, run by Amgen at 17 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extensive-Stage Small-Cell Lung Cancer
- What is being tested?
- Carfilzomib, Carboplatin and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 17 sitesin 3 countries
- Study dates
- 5 Nov 2013to 4 May 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United States11 sites
Levine Cancer Institute
Charlotte, North Carolina
Frederick Memorial Hospital
Frederick, Maryland
UF Health Davis Cancer Pavilion and Shands Med Plaza
Gainesville, Florida
Goshen Center for Cancer Care
Goshen, Indiana
John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey
The University of Texas MD Anderson Cancer Center
Houston, Texas
Horizon Oncology Research, Inc.
Lafayette, Indiana
Baptist Health Lexington Clinical Research Center
Lexington, Kentucky
Indiana University Health Ball Memorial Hospital
Muncie, Indiana
Yale University, Yale Cancer Center
New Haven, Connecticut
Wake Forest Baptist Health
Winston-Salem, North Carolina
Russia5 sites
State budgetary healthcare institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"
Arkhangelsk
Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
Kislino, Kursk Oblast
Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center"
Moscow
State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University"
Saint Petersburg
State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"
Yaroslavl
About this study
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
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).
- Conditions
- Extensive-Stage Small-Cell Lung Cancer
- Being tested
- Carfilzomib, Carboplatin, Etoposide
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called PR-171, PR171, Kyprolis®
Administered by intravenous infusion.
CarboplatinDrug
Administered by intravenous infusion.
EtoposideDrug
Administered by intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib Combination | Experimental | 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. Receives: Drug: Carfilzomib; Drug: Carboplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: First 21-day Cycle
Secondary outcomes (5)
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Cycle 1 Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2013 (estimated)
- Study start5 Nov 2013
- Primary completionAug 2016
- Study completion4 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Extensive-Stage Small-Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01987232
- Sponsor's protocol ID
- CFZ004
- Other IDs
- 2013-002597-44, 20130399
- Status last verified
- Jul 2017
- First submitted
- 6 Nov 2013
- Last updated
- 28 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01987232
- Acronym / sponsor ID
- CFZ004
- Conditions
- Extensive-Stage Small-Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 5 Nov 2013
- Primary completion
- Aug 2016 (actual)
- Study completion
- 4 May 2017 (actual)
- First posted
- 19 Nov 2013 (estimated)
- Results
- Posted 28 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib Combination | Experimental | Drug: Carfilzomib, Drug: Carboplatin, Drug: EtoposideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: PR-171, PR171, Kyprolis®Administered by intravenous infusion. | Drug | Carfilzomib Combination |
| CarboplatinAdministered by intravenous infusion. | Drug | Carfilzomib Combination |
| EtoposideAdministered by intravenous infusion. | Drug | Carfilzomib Combination |
Primary outcome
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.
5 secondary outcomes
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.
Overall Survival (OS) - Phase 2
Time frame: 30 months
Maximum Plasma Concentration - Phase 2
Time frame: Cycle 1 Day 2
Time of Maximum Plasma Concentration - Phase 2
Time frame: Cycle 1 Day 2
Area Under Plasma Concentration-Time Curve - Phase 2
Time frame: Cycle 1 Day 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Carfilzomib, Carboplatin and Etoposide in people with Extensive-Stage Small-Cell Lung Cancer, run by Amgen at 17 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Russia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (time frame: First 21-day Cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2017.