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

Tenosynovial Giant Cell Tumor Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02471716
• Other study ID #: FPA008-002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2015
• Est. completion date: April 30, 2020

Study information

• Verified date: July 2020
• Source: Five Prime Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of cabiralizumab in PVNS/dt-TGCT patients.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: April 30, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Pigmented Villonodular Synovitis
• Synovitis
• Synovitis, Pigmented Villonodular
• Tenosynovial Giant Cell Tumor

Intervention

Biological:
• FPA008
FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks

Locations

Country	Name	City	State
France	Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest	Bordeaux
France	Centre Léon Bérard	Lyon
Korea, Republic of	Seoul National University Hospital	Seoul	Jongno-gu
Netherlands	Leiden University Medical Center	Leiden
Poland	Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie	Warsaw
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Oxford University Hospital NHS Trust	Oxford
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Sarcoma Oncology Research Center LLC	Santa Monica	California
United States	Stanford Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Five Prime Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	52 weeks
Primary	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)	52 weeks
Secondary	PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)	Area under serum concentration-time curve (AUC) for cabiralizumab as a PK parameter	52 weeks
Secondary	Maximum Serum Concentration (Cmax).	Composite PK parameters of cabiralizumab: Maximum observed serum concentration	52 weeks
Secondary	Minimum Serum Concentration (Cmin).	Composite PK parameters of cabiralizumab: minimum serum concentration (Cmin).	52 weeks
Secondary	Pharmacokinetic Clearance (CL).	Composite PK parameters of cabiralizumab: clearance (CL)	52 weeks
Secondary	The Incidence of AEs.	treatment-emergent adverse events (TEAEs) by incidence for the Safety Population. Patients with at lease 1 TEAE.	52 weeks
Secondary	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	52 weeks
Secondary	The Incidence of ECG Abnormalities.	The number of patients who had a change in their ECG that were clinically significant	52 weeks
Secondary	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	52 weeks