Pigmented Villonodular SynovitisPhase 1/2FPA008-002NCT02471716
Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor
A Phase 1/2 study testing FPA008 in people with Pigmented Villonodular Synovitis and Tenosynovial Giant Cell Tumor, run by Five Prime Therapeutics, Inc. at 12 sites in 6 countries.
Trial summary
This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of cabiralizumab in PVNS/dt-TGCT patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor
- What is being tested?
- FPA008
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 12 sitesin 6 countries
- Study dates
- Jun 2015to 30 Apr 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
12 sites in 6 countries.
12 sites in 6 countries
United States5 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Sarcoma Oncology Research Center LLC
Santa Monica, California, 90403
Stanford Medicine
Stanford, California, 94301-5821
France2 sites
Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest
Bordeaux, 33076
Centre Léon Bérard
Lyon, 69008
United Kingdom2 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2TH
Oxford University Hospital NHS Trust
Oxford, OX3 7LE
Poland1 site
Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
Warsaw, 02-781
South Korea1 site
Seoul National University Hospital
Seoul, Jongno-gu, 110-744
About this study
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)
This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of cabiralizumab in PVNS/dt-TGCT patients.
Read the 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).
- Being tested
- FPA008
- Keywords
- Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)
- Medical subject headings
- Synovitis, Pigmented Villonodular, Giant Cell Tumor of Tendon Sheath
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FPA008Biological
Also called Cabiralizumab
FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 FPA008 Dose Escalation | Experimental | 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. Receives: Biological: FPA008 |
| Phase 2 FPA008 Dose Expansion | Experimental | 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. Receives: Biological: FPA008 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 52 weeks
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)
Measured: 52 weeks
Secondary outcomes (8)
PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)
Area under serum concentration-time curve (AUC) for cabiralizumab as a PK parameter
Measured: 52 weeks
Maximum Serum Concentration (Cmax).
Composite PK parameters of cabiralizumab: Maximum observed serum concentration
Measured: 52 weeks
Minimum Serum Concentration (Cmin).
Composite PK parameters of cabiralizumab: minimum serum concentration (Cmin).
Measured: 52 weeks
Pharmacokinetic Clearance (CL).
Composite PK parameters of cabiralizumab: clearance (CL)
Measured: 52 weeks
The Incidence of AEs.
treatment-emergent adverse events (TEAEs) by incidence for the Safety Population. Patients with at lease 1 TEAE.
Measured: 52 weeks
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
Measured: 52 weeks
The Incidence of ECG Abnormalities.
The number of patients who had a change in their ECG that were clinically significant
Measured: 52 weeks
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
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startJun 2015
- Primary completion30 Apr 2020
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pigmented Villonodular SynovitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Five Prime Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Lead, Study director, Five Prime Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02471716
- Sponsor's protocol ID
- FPA008-002
- Acronym
- FPA008-002
- Status last verified
- Jul 2020
- First submitted
- 1 Jun 2015
- Last updated
- 31 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02471716
- Acronym / sponsor ID
- FPA008-002 / FPA008-002
- Keywords
- Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Five Prime Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2015 (actual)
- Primary completion
- 30 Apr 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Posted 31 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 FPA008 Dose Escalation | Experimental | Biological: FPA008IV 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. |
| Phase 2 FPA008 Dose Expansion | Experimental | Biological: FPA008IV 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FPA008Also: CabiralizumabFPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks | Biological | Phase 1 FPA008 Dose Escalation, Phase 2 FPA008 Dose Expansion |
Primary outcome
The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1
Time frame: 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)
Time frame: 52 weeks
Number of confirmed objective responses (ORR) as assessed by the investigator per RECIST 1.1 (Phase 2)
8 secondary outcomes
PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)
Time frame: 52 weeks
Maximum Serum Concentration (Cmax).
Time frame: 52 weeks
Minimum Serum Concentration (Cmin).
Time frame: 52 weeks
Pharmacokinetic Clearance (CL).
Time frame: 52 weeks
The Incidence of AEs.
Time frame: 52 weeks
The Incidence of Clinical Laboratory Abnormalities.
Time frame: 52 weeks
The Incidence of ECG Abnormalities.
Time frame: 52 weeks
Duration of Response Per RECIST 1.1 in Phase 2
Time frame: 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Lead study director
Five Prime Therapeutics, Inc.
12 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FPA008 in people with Pigmented Villonodular Synovitis and Tenosynovial Giant Cell Tumor, run by Five Prime Therapeutics, Inc. at 12 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, France, United Kingdom, Netherlands, Poland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1 (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2021.