Phase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Patients With Previously Untreated Extensive Stage Small-cell Lung Cancer
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01987232
Collaborator
(none)
32
17
1
41.9
1.9
0
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date
:
Nov 5, 2013
Actual Primary Completion Date
:
Aug 1, 2016
Actual Study Completion Date
:
May 4, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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:
Drug: Carboplatin
Administered by intravenous infusion.
Drug: Etoposide
Administered by intravenous infusion.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-limiting Toxicities [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.
Secondary Outcome Measures
- Number of Participants With Adverse Events (AEs) [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.
- Overall Survival (OS) - Phase 2 [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.
- Maximum Plasma Concentration - Phase 2 [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.
- Time of Maximum Plasma Concentration - Phase 2 [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.
- Area Under Plasma Concentration-Time Curve - Phase 2 [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.
Other Outcome Measures
- Progression-free Survival [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.
- Overall Response Rate [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.
- Duration of Response [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale University, Yale Cancer Center | New Haven | Connecticut | United States | |
| 2 | UF Health Davis Cancer Pavilion and Shands Med Plaza | Gainesville | Florida | United States | |
| 3 | Goshen Center for Cancer Care | Goshen | Indiana | United States | |
| 4 | Horizon Oncology Research, Inc. | Lafayette | Indiana | United States | |
| 5 | Indiana University Health Ball Memorial Hospital | Muncie | Indiana | United States | |
| 6 | Baptist Health Lexington Clinical Research Center | Lexington | Kentucky | United States | |
| 7 | Frederick Memorial Hospital | Frederick | Maryland | United States | |
| 8 | John Theurer Cancer Center at Hackensack UMC | Hackensack | New Jersey | United States | |
| 9 | Levine Cancer Institute | Charlotte | North Carolina | United States | |
| 10 | Wake Forest Baptist Health | Winston-Salem | North Carolina | United States | |
| 11 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | |
| 12 | Juravinski Cancer Centre | Hamilton | Ontario | Canada | |
| 13 | Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary" | Kislino | Kursk | Russian Federation | |
| 14 | State budgetary healthcare institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary" | Arkhangelsk | Russian Federation | ||
| 15 | Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center" | Moscow | Russian Federation | ||
| 16 | State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University" | St. Petersburg | Russian Federation | ||
| 17 | State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital" | Yaroslavl | Russian Federation |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01987232
Other Study ID Numbers:
- CFZ004
- 2013-002597-44
- 20130399
First Posted:
Nov 19, 2013
Last Update Posted:
Aug 28, 2017
Last Verified:
Jul 1, 2017
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 17 centers in the United States, Russia, and Canada. |
|---|---|
| Pre-assignment Detail | In the phase 1b portion of the study participants were assigned sequentially to escalating doses of carfilzomib given in combination with standard dose carboplatin and etoposide to establish the maximum tolerated dose (MTD). The phase 2 portion of the study was not enrolled. |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, 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, and 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. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Period Title: Overall Study | |||||
| STARTED | 5 | 3 | 3 | 15 | 6 |
| COMPLETED | 5 | 3 | 3 | 14 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Total of all reporting groups |
| Overall Participants | 5 | 3 | 3 | 15 | 6 | 32 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
69.2
(13.8)
|
62.3
(8.5)
|
59.0
(7.5)
|
56.9
(9.4)
|
58.8
(7.9)
|
59.9
(10.1)
|
| Age, Customized (Count of Participants) | ||||||
| < 65 years |
2
40%
|
2
66.7%
|
2
66.7%
|
14
93.3%
|
5
83.3%
|
25
78.1%
|
| ≥ 65 years |
3
60%
|
1
33.3%
|
1
33.3%
|
1
6.7%
|
1
16.7%
|
7
21.9%
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
3
60%
|
2
66.7%
|
1
33.3%
|
5
33.3%
|
1
16.7%
|
12
37.5%
|
| Male |
2
40%
|
1
33.3%
|
2
66.7%
|
10
66.7%
|
5
83.3%
|
20
62.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
1
3.1%
|
| Not Hispanic or Latino |
5
100%
|
3
100%
|
3
100%
|
14
93.3%
|
5
83.3%
|
30
93.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
3.1%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| White |
5
100%
|
3
100%
|
3
100%
|
14
93.3%
|
6
100%
|
31
96.9%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
1
3.1%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | ||||||
| 0 (Fully active) |
4
80%
|
0
0%
|
1
33.3%
|
3
20%
|
2
33.3%
|
10
31.3%
|
| 1 (Restrictive but ambulatory) |
1
20%
|
3
100%
|
2
66.7%
|
12
80%
|
4
66.7%
|
22
68.8%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 5 | 3 | 3 | 15 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 5 | 3 | 3 | 15 | 6 |
| Any adverse event |
5
100%
|
3
100%
|
3
100%
|
15
100%
|
5
83.3%
|
| Adverse events ≥ grade 3 |
3
60%
|
3
100%
|
2
66.7%
|
13
86.7%
|
4
66.7%
|
| Serious adverse events |
1
20%
|
1
33.3%
|
1
33.3%
|
7
46.7%
|
2
33.3%
|
| AEs leading to disocontinuation of study drug |
1
20%
|
0
0%
|
0
0%
|
3
20%
|
1
16.7%
|
| Fatal adverse events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants enrolled in phase 2 |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 participants |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 participants |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 participants |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 5 | 3 | 3 | 15 | 6 | 32 |
| Median (95% Confidence Interval) [months] |
4.0
|
6.4
|
7.0
|
2.9
|
3.8
|
4.4
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study treatment. |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target area AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 5 | 3 | 3 | 15 | 6 | 32 |
| Number (95% Confidence Interval) [percentage of participants] |
60.0
1200%
|
100.0
3333.3%
|
66.7
2223.3%
|
33.3
222%
|
33.3
555%
|
46.9
146.6%
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a confirmed response of PR or CR. |
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | All Participants |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. |
| Measure Participants | 3 | 3 | 2 | 5 | 2 | 15 |
| Median (95% Confidence Interval) [months] |
4.9
|
5.0
|
NA
|
4.3
|
4.5
|
4.8
|
Adverse Events
| Time Frame | From first day of any study treatment (i.e., carfilzomib, carboplatin, or etoposide), and within 30 days of the last day of study treatment. The median overall duration of treatment was 16 weeks. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. | |||||||||
| Arm/Group Title | Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | |||||
| Arm/Group Description | Participants received carfilzomib 20 mg/m² on days 2, 3, 9, and 10 of each 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 27 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each 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. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 36 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 45 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | Participants received carfilzomib 20 mg/m² on cycle 1 days 2 and 3, then 56 mg/m² on days 9 and 10 and thereafter for each subsequent 21-day cycle, carboplatin at a target AUC of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, and 3 of each cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until PD, unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest. | |||||
All Cause Mortality |
||||||||||
| Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/5 (20%) | 1/3 (33.3%) | 1/3 (33.3%) | 7/15 (46.7%) | 2/6 (33.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Febrile neutropenia | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Infections and infestations | ||||||||||
| Clostridium difficile colitis | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Injection site abscess | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pneumonia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/15 (6.7%) | 1/6 (16.7%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Fluid overload | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Hypoalbuminaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Nervous system disorder | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Chronic obstructive pulmonary disease | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pulmonary embolism | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pulmonary haemorrhage | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Pulmonary oedema | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Vascular disorders | ||||||||||
| Peripheral artery thrombosis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Carfilzomib 20/20 mg/m² | Carfilzomib 20/27 mg/m² | Carfilzomib 20/36 mg/m² | Carfilzomib 20/45 mg/m² | Carfilzomib 20/56 mg/m² | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 3/3 (100%) | 3/3 (100%) | 15/15 (100%) | 5/6 (83.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 2/5 (40%) | 3/3 (100%) | 2/3 (66.7%) | 8/15 (53.3%) | 3/6 (50%) | |||||
| Leukocytosis | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Leukopenia | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 3/15 (20%) | 1/6 (16.7%) | |||||
| Neutropenia | 1/5 (20%) | 2/3 (66.7%) | 0/3 (0%) | 10/15 (66.7%) | 3/6 (50%) | |||||
| Thrombocytopenia | 0/5 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 7/15 (46.7%) | 4/6 (66.7%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear congestion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Ear discomfort | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Ear pain | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Hypoacusis | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Vertigo | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Abdominal distension | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Abdominal pain | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Constipation | 3/5 (60%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Diarrhoea | 1/5 (20%) | 2/3 (66.7%) | 1/3 (33.3%) | 5/15 (33.3%) | 0/6 (0%) | |||||
| Flatulence | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Haematochezia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Nausea | 3/5 (60%) | 3/3 (100%) | 3/3 (100%) | 5/15 (33.3%) | 1/6 (16.7%) | |||||
| Oesophagitis | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Stomatitis | 0/5 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Toothache | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Vomiting | 0/5 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 3/15 (20%) | 0/6 (0%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/15 (13.3%) | 1/6 (16.7%) | |||||
| Catheter site pain | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Chills | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Fatigue | 1/5 (20%) | 1/3 (33.3%) | 1/3 (33.3%) | 4/15 (26.7%) | 2/6 (33.3%) | |||||
| Mucosal inflammation | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Non-cardiac chest pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Oedema peripheral | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 2/15 (13.3%) | 1/6 (16.7%) | |||||
| Pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pyrexia | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 2/15 (13.3%) | 1/6 (16.7%) | |||||
| Immune system disorders | ||||||||||
| Hypersensitivity | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Infections and infestations | ||||||||||
| Cellulitis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Clostridium difficile colitis | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Influenza | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Injection site infection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Lower respiratory tract infection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Lung infection | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Mucosal infection | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Oral candidiasis | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Oral herpes | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Pneumonia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Respiratory tract infection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Sinusitis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Skin infection | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Upper respiratory tract infection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Vulvovaginal candidiasis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Vulvovaginal mycotic infection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Fall | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Head injury | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Incision site erythema | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Incision site swelling | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Infusion related reaction | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Laceration | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Wound | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Aspartate aminotransferase increased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Blood alkaline phosphatase increased | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Blood creatinine increased | 0/5 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/15 (6.7%) | 2/6 (33.3%) | |||||
| Blood glucose increased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Blood phosphorus increased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Blood potassium decreased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Blood urea increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Blood uric acid increased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Creatinine renal clearance decreased | 2/5 (40%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 2/6 (33.3%) | |||||
| Ejection fraction decreased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Haemoglobin decreased | 1/5 (20%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Neutrophil count decreased | 1/5 (20%) | 2/3 (66.7%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Platelet count decreased | 0/5 (0%) | 2/3 (66.7%) | 0/3 (0%) | 2/15 (13.3%) | 2/6 (33.3%) | |||||
| Weight decreased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Weight increased | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| White blood cell count decreased | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/15 (6.7%) | 1/6 (16.7%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 2/5 (40%) | 0/3 (0%) | 2/3 (66.7%) | 2/15 (13.3%) | 1/6 (16.7%) | |||||
| Dehydration | 1/5 (20%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Diabetes mellitus | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Gout | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Hyperglycaemia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Hyperkalaemia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Hypoalbuminaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Hypocalcaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Hypoglycaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Hypokalaemia | 1/5 (20%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Hypomagnesaemia | 0/5 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Hyponatraemia | 0/5 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Metabolic acidosis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 3/15 (20%) | 0/6 (0%) | |||||
| Bone pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 1/6 (16.7%) | |||||
| Costochondritis | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Groin pain | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Muscular weakness | 0/5 (0%) | 0/3 (0%) | 2/3 (66.7%) | 3/15 (20%) | 0/6 (0%) | |||||
| Musculoskeletal chest pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Musculoskeletal pain | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Neck pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pain in extremity | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Cancer pain | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Nervous system disorders | ||||||||||
| Ageusia | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Cerebrovascular accident | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Decreased vibratory sense | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Dizziness | 0/5 (0%) | 1/3 (33.3%) | 2/3 (66.7%) | 3/15 (20%) | 1/6 (16.7%) | |||||
| Dysgeusia | 1/5 (20%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Headache | 0/5 (0%) | 2/3 (66.7%) | 2/3 (66.7%) | 3/15 (20%) | 0/6 (0%) | |||||
| Hypoaesthesia | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Hyporeflexia | 1/5 (20%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Neuropathy peripheral | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Paraesthesia | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Peripheral sensory neuropathy | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Tremor | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Vocal cord paralysis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Confusional state | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Depression | 1/5 (20%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Insomnia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Dysuria | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Micturition disorder | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Breast pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Aspiration | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Cough | 1/5 (20%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/15 (6.7%) | 1/6 (16.7%) | |||||
| Dry throat | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Dyspnoea | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 2/15 (13.3%) | 1/6 (16.7%) | |||||
| Haemoptysis | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/15 (13.3%) | 0/6 (0%) | |||||
| Hypoxia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Nasal congestion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Oropharyngeal pain | 1/5 (20%) | 1/3 (33.3%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pleural effusion | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Pulmonary embolism | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Pulmonary oedema | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Rhinorrhoea | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Wheezing | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 1/5 (20%) | 0/3 (0%) | 2/3 (66.7%) | 5/15 (33.3%) | 1/6 (16.7%) | |||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Pruritus | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Rash | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Rash macular | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Skin discolouration | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Skin irritation | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
| Swelling face | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Flushing | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Hypertension | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 1/15 (6.7%) | 0/6 (0%) | |||||
| Hypotension | 1/5 (20%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 1/6 (16.7%) | |||||
| Jugular vein thrombosis | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Orthostatic hypotension | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/15 (0%) | 0/6 (0%) | |||||
| Phlebitis | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/15 (0%) | 0/6 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01987232
Other Study ID Numbers:
- CFZ004
- 2013-002597-44
- 20130399
First Posted:
Nov 19, 2013
Last Update Posted:
Aug 28, 2017
Last Verified:
Jul 1, 2017