Trial Outcomes & Findings for A Study of Extended Carfilzomib Therapy for Patients Previously Enrolled in Carfilzomib Treatment Protocols (NCT NCT00884312)

Last Updated: 2018-05-14

Results Overview

Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

101 participants

Primary outcome timeframe

From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Results posted on

2018-05-14

Participant Flow

This study was conducted at 23 centers in the United States and Canada from April 2009 to May 2017.

Participant milestones

Participant milestones
Measure	Solid Tumors Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Overall Study STARTED	9	92
Overall Study Received Treatment	9	91
Overall Study COMPLETED	7	67
Overall Study NOT COMPLETED	2	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Solid Tumors Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Overall Study Non-fatal Progressive Disease	0	8
Overall Study Fatal Progressive Disease	0	1
Overall Study Non-fatal Adverse Event	1	0
Overall Study Fatal Adverse Event	1	4
Overall Study Withdrawal by Subject	0	6
Overall Study Physician Decision	0	1
Overall Study Other	0	4
Overall Study Did Not Receive Study Drug	0	1

Baseline Characteristics

A Study of Extended Carfilzomib Therapy for Patients Previously Enrolled in Carfilzomib Treatment Protocols

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Solid Tumors n=9 Participants Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma n=91 Participants Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Total n=100 Participants Total of all reporting groups
Age, Continuous	61.2 years STANDARD_DEVIATION 12.75 • n=5 Participants	63.2 years STANDARD_DEVIATION 9.82 • n=7 Participants	63.0 years STANDARD_DEVIATION 10.05 • n=5 Participants
Age, Customized < 65 years	5 Participants n=5 Participants	47 Participants n=7 Participants	52 Participants n=5 Participants
Age, Customized ≥ 65 years	4 Participants n=5 Participants	44 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	38 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	53 Participants n=7 Participants	56 Participants n=5 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	71 Participants n=7 Participants	80 Participants n=5 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	6 Participants n=5 Participants	39 Participants n=7 Participants	45 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restricted but ambulatory)	3 Participants n=5 Participants	42 Participants n=7 Participants	45 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory but unable to work)	0 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Population: All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.

Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain.

Outcome measures

Outcome measures
Measure	Solid Tumors n=9 Participants Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma n=91 Participants Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Number of Participants With Peripheral Neuropathy	1 participants	15 participants

PRIMARY outcome

Population: All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.

Adverse events (AEs) were assigned a severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale version 3.0. Per protocol, adverse events were collected if they led to dose modification or dose discontinuation, were grade ≥ 3 or serious, or were events of peripheral neuropathy (any grade). A serious AE is one 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 in the offspring of an exposed subject * Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above.

Outcome measures

Outcome measures
Measure	Solid Tumors n=9 Participants Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma n=91 Participants Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Number of Participants With Adverse Events Any adverse event	7 participants	84 participants
Number of Participants With Adverse Events Adverse event ≥ grade 3	5 participants	66 participants
Number of Participants With Adverse Events Serious adverse events	5 participants	57 participants
Number of Participants With Adverse Events Fatal adverse events	1 participants	7 participants
Number of Participants With Adverse Events AE leading to discontinuation of carfilzomib	5 participants	20 participants

SECONDARY outcome

Population: All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.

Since participants were only followed up to 30 days after administration of last dose of study drug per protocol, Kaplan-Meier estimates of overall survival were not calculated. The number of participants who died within 30 days after administration of last dose of study drug is reported.

Outcome measures

Outcome measures
Measure	Solid Tumors n=9 Participants Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma n=91 Participants Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Overall Survival	1 participants	7 participants

SECONDARY outcome

Timeframe: From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Population: Enrolled participants excluding those with no postbaseline endpoint data subsequent to at least 1 dose of the study drug on the PX-171-010 protocol and participants who lacked baseline data for those analyses that required baseline data. Only participants with regimens that continued from the initial study without baseline being reset are included.

Progression-free survival (PFS) was defined as the time between the start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurred first. Disease progression was determined by the local investigator for regimens with the same baseline using the International Uniform Response Criteria (IMWG-URC) for participants with multiple myeloma and Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid tumor participants. PFS was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.

Outcome measures

Outcome measures
Measure	Solid Tumors n=6 Participants Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma n=58 Participants Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Progression-free Survival	41.9 months In this cohort participants were not followed until confirmed progressive disease. Only one participant was followed until an event; therefore PFS data were not mature and confidence interval could not be calculated.	19.6 months Interval 10.2 to 30.6

SECONDARY outcome

Population: Enrolled participants excluding those with no postbaseline endpoint data subsequent to at least 1 dose of the study drug on the PX-171-010 protocol and participants who lacked baseline data for those analyses that required baseline data Only participants with regimens that continued from the initial study without baseline being reset are included.

Time to progression (TTP) was defined as the time between start of treatment to the first documentation of disease progression. TTP was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.

Outcome measures

Outcome measures
Measure	Solid Tumors n=6 Participants Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Multiple Myeloma n=58 Participants Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Time to Progression	NA months Could not be estimated due to the low number of events	19.6 months Interval 10.2 to 30.6

Adverse Events

Solid Tumors

Serious events: 5 serious events

Other events: 6 other events

Deaths: 1 deaths

Multiple Myeloma

Serious events: 57 serious events

Other events: 69 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER