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

Phase 1

Completed

• Conditions: Pigmented Villonodular Synovitis; Tenosynovial Giant Cell Tumor
• Interventions: Biological: FPA008

• Registration Number: NCT02471716
• Lead Sponsor: Five Prime Therapeutics, Inc.

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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-01
• Study First Submitted QC: 2015-06-10
• Study First Posted: 2015-06-15
• Primary Completion: 2020-04-30
• Study Completion: 2020-04-30
• Status Verified: 2020-07
• Results First Submitted: 2021-08-04
• Results First Submitted QC: 2021-08-04
• Last Update Submitted: 2021-08-04
• Results First Posted: 2021-08-31
• Last Update Posted: 2021-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 FPA008 Dose Expansion	FPA008	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.
Phase 1 FPA008 Dose Escalation	FPA008	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.

Primary Outcome Measures

Name	Time	Method
The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1	52 weeks	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)	52 weeks	Number of confirmed objective responses (ORR) as assessed by the investigator per RECIST 1.1 (Phase 2)

Secondary Outcome Measures

Name	Time	Method
PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)	52 weeks	Area under serum concentration-time curve (AUC) for cabiralizumab as a PK parameter
Maximum Serum Concentration (Cmax).	52 weeks	Composite PK parameters of cabiralizumab: Maximum observed serum concentration
Duration of Response Per RECIST 1.1 in Phase 2	52 weeks	The length of response per RECIST 1.1 from the time of first response to progression or going off study in Phase 2
Pharmacokinetic Clearance (CL).	52 weeks	Composite PK parameters of cabiralizumab: clearance (CL)
The Incidence of Clinical Laboratory Abnormalities.	52 weeks	The number of patients with a clinical laboratory that is outside the normal range at some time point during the study
Minimum Serum Concentration (Cmin).	52 weeks	Composite PK parameters of cabiralizumab: minimum serum concentration (Cmin).
The Incidence of AEs.	52 weeks	treatment-emergent adverse events (TEAEs) by incidence for the Safety Population. Patients with at lease 1 TEAE.
The Incidence of ECG Abnormalities.	52 weeks	The number of patients who had a change in their ECG that were clinically significant

Trial Locations

Locations (12)

Centre Léon Bérard; 🇫🇷 Lyon, France

University Hospitals Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

The University of Texas, MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sarcoma Oncology Research Center LLC; 🇺🇸 Santa Monica, California, United States

Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest; 🇫🇷 Bordeaux, France

Stanford Medicine; 🇺🇸 Stanford, California, United States

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie; 🇵🇱 Warsaw, Poland

Oxford University Hospital NHS Trust; 🇬🇧 Oxford, United Kingdom

Seoul National University Hospital; 🇰🇷 Seoul, Jongno-gu, Korea, Republic of