Study of FPA008 in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02471716
Recruitment Status : Recruiting
First Posted : June 15, 2015
Last Update Posted : April 27, 2018
Information provided by (Responsible Party):
Five Prime Therapeutics, Inc.

Brief Summary:
This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of FPA008 in PVNS/dt-TGCT patients. Patients will be enrolled into either Phase 1 (dose escalation) or Phase 2 (dose expansion) of the study, but not both.

Condition or disease Intervention/treatment Phase
Pigmented Villonodular Synovitis Tenosynovial Giant Cell Tumor Drug: FPA008 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of FPA008, an Anti-CSF1 Receptor Antibody, in Patients With Pigmented Villonodular Synovitis (PVNS)/ Diffuse Type Tenosynovial Giant Cell Tumor (Dt-TGCT)
Study Start Date : June 2015
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Phase 1 FPA008 Dose Escalation
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.
Drug: FPA008
FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks
Experimental: Phase 2 FPA008 Dose Expansion
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.
Drug: FPA008
FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks

Primary Outcome Measures :
  1. The incidence of Grade 3 and Grade 4 adverse events (AEs) defined as dose-limiting toxicities (Phase 1) [ Time Frame: 52 weeks ]
  2. The incidence of clinical laboratory abnormalities defined as dose-limiting toxicities (Phase 1) [ Time Frame: 52 weeks ]
  3. The incidence of confirmed objective responses per RECIST 1.1 (Phase 2) [ Time Frame: 52 weeks ]

Secondary Outcome Measures :
  1. Composite PK parameters of FPA008: area under serum concentration-time curve (AUC), maximum serum concentration (Cmax), minimum serum concentration (Cmin), and clearance (CL); additional PK parameters as appropriate. [ Time Frame: 52 weeks ]
  2. The incidence of AEs. [ Time Frame: 52 weeks ]
  3. The incidence of clinical laboratory abnormalities. [ Time Frame: 52 weeks ]
  4. The incidence of ECG abnormalities. [ Time Frame: 52 weeks ]
  5. Duration of response per RECIST 1.1 [ Time Frame: 52 weeks ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02471716

Contact: Medical Lead

United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Principal Investigator: K.Kumar Sankhala         
Sarcoma Oncology Research Center LLC Recruiting
Santa Monica, California, United States, 90403
Principal Investigator: Sant P Chawla, MD         
Stanford Medicine Recruiting
Stanford, California, United States, 94301-5821
Principal Investigator: Kristen N Ganjoo, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Andrew J. Wagner, MD, PhD         
United States, Texas
The University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Vinod Ravi, MD         
Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest Recruiting
Bordeaux, France, 33076
Principal Investigator: Italiano Antoine, MD         
Centre Léon Bérard Recruiting
Lyon, France, 69008
Principal Investigator: Blay Jean-Yves, MD         
Korea, Republic of
Seoul National University Hospital Completed
Seoul, Jongno-gu, Korea, Republic of, 110-744
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2333 ZA
Principal Investigator: Andre J Gelderblom, MD         
Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie Recruiting
Warsaw, Poland, 02-781
Principal Investigator: Piotr Rutkowski, MD, PhD         
United Kingdom
University Hospitals Birmingham NHS Foundation Trust Completed
Birmingham, United Kingdom, B15 2TH
Oxford University Hospital NHS Trust Completed
Oxfordshire, United Kingdom, OX3 7LE
Sponsors and Collaborators
Five Prime Therapeutics, Inc.
Study Director: Medical Lead Five Prime Therapeutics, Inc.

Responsible Party: Five Prime Therapeutics, Inc. Identifier: NCT02471716     History of Changes
Other Study ID Numbers: FPA008-002
First Posted: June 15, 2015    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018

Keywords provided by Five Prime Therapeutics, Inc.:
Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)

Additional relevant MeSH terms:
Giant Cell Tumors
Giant Cell Tumor of Tendon Sheath
Synovitis, Pigmented Villonodular
Joint Diseases
Musculoskeletal Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Muscular Diseases