Clinical trial NCT02471716: Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor
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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pigmented Villonodular Synovitis
Tenosynovial Giant Cell Tumor
Keywords: Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)
Lead sponsor: Five Prime Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-15
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1
timeFrame: 52 weeks
measure: The Incidence of Investigator-assessed, Confirmed Objective Responses (ORR) Per RECIST 1.1 (Phase 2)
timeFrame: 52 weeks
Secondary outcomes:
measure: PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)
timeFrame: 52 weeks
measure: Maximum Serum Concentration (Cmax).
timeFrame: 52 weeks
measure: Minimum Serum Concentration (Cmin).
timeFrame: 52 weeks
measure: Pharmacokinetic Clearance (CL).
timeFrame: 52 weeks
measure: The Incidence of AEs.
timeFrame: 52 weeks
measure: The Incidence of Clinical Laboratory Abnormalities.
timeFrame: 52 weeks
measure: The Incidence of ECG Abnormalities.
timeFrame: 52 weeks
measure: Duration of Response Per RECIST 1.1 in Phase 2
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center LLC
state: California
city: Stanford
country: United States
facility: Stanford Medicine
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Bordeaux
country: France
facility: Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest
city: Lyon
country: France
facility: Centre Léon Bérard
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Warsaw
country: Poland
facility: Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospital NHS Trust
Study officials:
affiliation: Five Prime Therapeutics, Inc.
name: Medical Lead
role: STUDY_DIRECTOR
References: