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

Phase 1

Completed

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).

Recruitment & 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

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

Locations (12): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Sarcoma Oncology Research Center LLC
🇺🇸
Santa Monica, California, United States
Stanford Medicine
🇺🇸
Stanford, California, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
The University of Texas, MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest
🇫🇷
Bordeaux, France
Centre Léon Bérard
🇫🇷
Lyon, France
Seoul National University Hospital
🇰🇷
Seoul, Jongno-gu, Korea, Republic of
Leiden University Medical Center
🇳🇱
Leiden, Netherlands
Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
🇵🇱
Warsaw, Poland
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Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States