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

An Open-Label, Single-Arm, Phase 2 Study of Extended Carfilzomib Therapy in Subjects Previously Enrolled in Carfilzomib Treatment Protocols

This is a multi-center, open-label, Phase 2 study of carfilzomib to monitor the safety and efficacy of long-term or continuing carfilzomib therapy for patients who previously completed a primary carfilzomib treatment study.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Solid Tumors
• Intervention / Treatment: Drug: Carfilzomib

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University of Toronto, Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Pinnacle Oncology Hematology
  • California
    • Beverly Hills, California, United States, 90211
      • Tower Cancer Research Foundation
    • Duarte, California, United States, 91010
      • City of Hope National Medial Center
    • San Francisco, California, United States, 94143
      • University of California Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute - Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Greenebaum Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1093
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack UMC
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
      • Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center
    • Houston, Texas, United States, 77090
      • Northwest Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Previous completion of a carfilzomib study within 90 days prior to first dose of maintenance study drug.
2. Disease Assessments performed within 30 days prior to first dose of maintenance study drug.
3. Written informed consent in accordance with federal, local, and institutional guidelines
4. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL, within 3 days prior to first dose of maintenance study drug.
5. Subjects must agree to adhere to the study visit schedule and other study requirements and receive outpatient treatment and laboratory monitoring at the institution that administers the drug.

Exclusion Criteria:

1. Administration of an intervening chemotherapy between the time of previous carfilzomib study termination and first dose of maintenance study drug.
2. Pregnant or lactating females
3. Diagnosis of a new malignancy of a different tumor type.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Carfilzomib; Participants 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.

Drug: Carfilzomib; Carfilzomib dose levels ranged from 11 to 27 mg/m² for 2- to 10-minute infusions and 36 to 56 mg/m² for 30-minute infusions. Carfilzomib doses were administered on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Dose level reduction to a minimum dose of 11 mg/m² for toxicity was permitted.; Other Names: PR-171; Kyprolis®; PR171

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Peripheral Neuropathy	Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain.	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.
Number of Participants With Adverse Events	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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.	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.
Progression-free Survival	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.	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.
Time to Progression	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.	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.

Collaborators and Investigators

• Sponsor: Amgen

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2009
• Primary Completion (Actual): May 17, 2017
• Study Completion (Actual): May 17, 2017

Study Registration Dates

• First Submitted: April 16, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (Estimate): April 20, 2009

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: April 9, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Multiple myeloma; Hematological; proteasome; carfilzomib; PR-171
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Multiple Myeloma
• Other Study ID Numbers: PX-171-010; 20130394 (Other Identifier: Amgen Study ID)