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Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor (FPA008-002)

Primary Purpose

Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
FPA008
Sponsored by
Five Prime Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pigmented Villonodular Synovitis focused on measuring Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed diagnosis of inoperable PVNS/ dt-TGCT or potentially resectable tumor that would result in unacceptable functional loss or morbidity as determined by a qualified surgeon or multi-disciplinary tumor board (must be documented in the CRF during screening)
  • Measurable PVNS/dt-TGCT by RECIST 1.1 on MRI
  • ECOG performance status <1

Exclusion Criteria:

  • Prior therapy with an anti-CSF1R antibody
  • Prior therapy with PLX3397 unless discontinued for intolerance (i.e., non-progression on prior kinase inhibitor)
  • Liver function tests (including ALT, AST, and total bilirubin), outside of the range of local laboratory normal at Screening
  • Inadequate organ or bone marrow function
  • History of congestive heart failure or myocardial infarction <1 year prior to first study dose administration
  • Significant abnormalities on ECG at Screening
  • Contraindications to MRI and use of intravenous gadolinium-based contrast agents
  • Creatine Kinase ≥ 1.5x the upper limit of normal
  • Positive test for latent TB at Screening (Quantiferon test)
  • Active known or suspected autoimmune disease

Sites / Locations

  • Cedars-Sinai Medical Center
  • Sarcoma Oncology Research Center LLC
  • Stanford Medicine
  • Dana-Farber Cancer Institute
  • The University of Texas, MD Anderson Cancer Center
  • Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest
  • Centre Léon Bérard
  • Seoul National University Hospital
  • Leiden University Medical Center
  • Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
  • University Hospitals Birmingham NHS Foundation Trust
  • Oxford University Hospital NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1 FPA008 Dose Escalation

Phase 2 FPA008 Dose Expansion

Arm Description

IV infusion; safety data will be reviewed prior to dose escalation decision. Dose escalation will complete when recommended dose (RD) is determined. RD will be the maximum tolerated dose or lower dose that provide adequate PK exposure and biologic activity with tolerability.

IV infusion; once MTD and/or RD has been determined in Phase 1, expansion cohorts of approximately 30 patients (each cohort) with PVNS or dt-TGCT will be enrolled to characterize clinical activity and safety profile of the RD. Treatment is planned to continue for up to 24 weeks or 56 weeks.

Outcomes

Primary Outcome Measures

The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1
Number of participants with grade 3 and grade 4 adverse events (AE) defined as dose limiting toxicities (DLTs) in Phase 1
The Incidence of Investigator-assessed, Confirmed Objective Responses (ORR) Per RECIST 1.1 (Phase 2)
Number of confirmed objective responses (ORR) as assessed by the investigator per RECIST 1.1 (Phase 2)

Secondary Outcome Measures

PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)
Area under serum concentration-time curve (AUC) for cabiralizumab as a PK parameter
Maximum Serum Concentration (Cmax).
Composite PK parameters of cabiralizumab: Maximum observed serum concentration
Minimum Serum Concentration (Cmin).
Composite PK parameters of cabiralizumab: minimum serum concentration (Cmin).
Pharmacokinetic Clearance (CL).
Composite PK parameters of cabiralizumab: clearance (CL)
The Incidence of AEs.
treatment-emergent adverse events (TEAEs) by incidence for the Safety Population. Patients with at lease 1 TEAE.
The Incidence of Clinical Laboratory Abnormalities.
The number of patients with a clinical laboratory that is outside the normal range at some time point during the study
The Incidence of ECG Abnormalities.
The number of patients who had a change in their ECG that were clinically significant
Duration of Response Per RECIST 1.1 in Phase 2
The length of response per RECIST 1.1 from the time of first response to progression or going off study in Phase 2

Full Information

First Posted
June 1, 2015
Last Updated
August 4, 2021
Sponsor
Five Prime Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02471716
Brief Title
Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor
Acronym
FPA008-002
Official Title
A Phase 1/2 Study of Cabiralizumab, an Anti-CSF1 Receptor Antibody, in Patients With Pigmented Villonodular Synovitis (PVNS)/ Diffuse Type Tenosynovial Giant Cell Tumor (Dt-TGCT)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
June 2015 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
April 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Five Prime Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of cabiralizumab in PVNS/dt-TGCT patients.
Detailed Description
A Phase 1/2 study was an open-label, dose escalation and dose expansion study designed to evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of cabiralizumab, a CSF1-R monoclonal antibody, inpatients with unresectable diffuse tenosynovial giant cell tumors (TGCT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor
Keywords
Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 FPA008 Dose Escalation
Arm Type
Experimental
Arm Description
IV infusion; safety data will be reviewed prior to dose escalation decision. Dose escalation will complete when recommended dose (RD) is determined. RD will be the maximum tolerated dose or lower dose that provide adequate PK exposure and biologic activity with tolerability.
Arm Title
Phase 2 FPA008 Dose Expansion
Arm Type
Experimental
Arm Description
IV infusion; once MTD and/or RD has been determined in Phase 1, expansion cohorts of approximately 30 patients (each cohort) with PVNS or dt-TGCT will be enrolled to characterize clinical activity and safety profile of the RD. Treatment is planned to continue for up to 24 weeks or 56 weeks.
Intervention Type
Biological
Intervention Name(s)
FPA008
Other Intervention Name(s)
Cabiralizumab
Intervention Description
FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks
Primary Outcome Measure Information:
Title
The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1
Description
Number of participants with grade 3 and grade 4 adverse events (AE) defined as dose limiting toxicities (DLTs) in Phase 1
Time Frame
52 weeks
Title
The Incidence of Investigator-assessed, Confirmed Objective Responses (ORR) Per RECIST 1.1 (Phase 2)
Description
Number of confirmed objective responses (ORR) as assessed by the investigator per RECIST 1.1 (Phase 2)
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)
Description
Area under serum concentration-time curve (AUC) for cabiralizumab as a PK parameter
Time Frame
52 weeks
Title
Maximum Serum Concentration (Cmax).
Description
Composite PK parameters of cabiralizumab: Maximum observed serum concentration
Time Frame
52 weeks
Title
Minimum Serum Concentration (Cmin).
Description
Composite PK parameters of cabiralizumab: minimum serum concentration (Cmin).
Time Frame
52 weeks
Title
Pharmacokinetic Clearance (CL).
Description
Composite PK parameters of cabiralizumab: clearance (CL)
Time Frame
52 weeks
Title
The Incidence of AEs.
Description
treatment-emergent adverse events (TEAEs) by incidence for the Safety Population. Patients with at lease 1 TEAE.
Time Frame
52 weeks
Title
The Incidence of Clinical Laboratory Abnormalities.
Description
The number of patients with a clinical laboratory that is outside the normal range at some time point during the study
Time Frame
52 weeks
Title
The Incidence of ECG Abnormalities.
Description
The number of patients who had a change in their ECG that were clinically significant
Time Frame
52 weeks
Title
Duration of Response Per RECIST 1.1 in Phase 2
Description
The length of response per RECIST 1.1 from the time of first response to progression or going off study in Phase 2
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed diagnosis of inoperable PVNS/ dt-TGCT or potentially resectable tumor that would result in unacceptable functional loss or morbidity as determined by a qualified surgeon or multi-disciplinary tumor board (must be documented in the CRF during screening) Measurable PVNS/dt-TGCT by RECIST 1.1 on MRI ECOG performance status <1 Exclusion Criteria: Prior therapy with an anti-CSF1R antibody Prior therapy with PLX3397 unless discontinued for intolerance (i.e., non-progression on prior kinase inhibitor) Liver function tests (including ALT, AST, and total bilirubin), outside of the range of local laboratory normal at Screening Inadequate organ or bone marrow function History of congestive heart failure or myocardial infarction <1 year prior to first study dose administration Significant abnormalities on ECG at Screening Contraindications to MRI and use of intravenous gadolinium-based contrast agents Creatine Kinase ≥ 1.5x the upper limit of normal Positive test for latent TB at Screening (Quantiferon test) Active known or suspected autoimmune disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Lead
Organizational Affiliation
Five Prime Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Sarcoma Oncology Research Center LLC
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
Stanford Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94301-5821
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
The University of Texas, MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Seoul National University Hospital
City
Seoul
State/Province
Jongno-gu
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Oxford University Hospital NHS Trust
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor

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