A trial to evaluate the safety and tolerability of FPA008 in a condition involving patients with joint disease (involving inflammation and overgrowth of the joint lining)
- Conditions
- Pigmented villonodular synovitis (PVNS)/Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)MedDRA version: 20.0Level: LLTClassification code 10047413Term: Villonodular synovitisSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000547-17-PL
- Lead Sponsor
- Five Prime Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
1. Understand and sign an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation
2. Age >=18 years
3. 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 determined in the CRF during screening)
4. Measurable PVNS/dt-TGCT by RECIST v1.1 on MRI
5. ECOG performance status <=1
6. Willing and able to comply with all study procedures
7. In sexually-active patients (i.e., females of childbearing potential, who have not undergone menopause as defined by 12 consecutive months of amenorrhea or had a permanent sterilization procedure and males, who have not had a permanent sterilization procedure), willingness to use 2 effective methods of contraception, of which one must be a physical barrier method (condom, diaphragm, or cervical/vault cap) during the study and until 6 months after the last dose of cabiralizumab. Other effective forms of contraception are permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral tubal ligation with surgery, or vasectomy) at least 6 months prior to Screening. Females <55 years of age should have FSH >40. Female patients of childbearing potential must be on stable oral contraceptive therapy or intrauterine or implant device for at least 90 days prior to the study, or abstain from sexual intercourse as a way of living.
8. Patients being retreated with cabiralizumab must have completed 6 cycles of initial treatment at the 1 mg/kg or 2 mg/kg dose levels and the End-of- Treatment Follow-Up Period.
Note: Prior to re-treatment, patients will be re-assessed to ensure they meet the same eligibility requirements as untreated patients.
9. Patients must have a minimum average Brief Pain Inventory (BPI) score of two points during screening (based on the average of questions 3-6 of the BPI, assessed for at least 5 of 14 days prior to C1D1; see Appendix 7).
10. Patients must be on a stable analgesic regimen for two weeks prior to first dose.
No waivers of these inclusion criteria will be granted.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19
Patients enrolling into Phase 1 or Phase 2 will be excluded if any of the following criteria apply:
1. Prior therapy with another anti-CSF1R antibody within three months of first study dose administration (Note: Patients that discontinued prior anti-CSF1R antibody due to a drug-related serious adverse events will not be permitted to enroll)
2. Prior therapy with pexidartinib (PLX3397), imatinib, or nilotinib within four weeks of first study dose administration
3. Liver function tests (including ALT, AST, and total bilirubin), outside of the range of local laboratory normal at Screening
4. Inadequate organ or bone marrow function defined as: hemoglobin < 10 g/dL, absolute neutrophil count <1.5x 10x9/L, platelet count <100x 10x9/L, serum creatinine >1.5x ULN or calculated creatinine clearance <30 mL/min
5. Any surgical procedure of the involved joint within 12 weeks prior to first study dose administration (except baseline synovium biopsy, if performed)
6. Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
7. History of congestive heart failure or myocardial infarction <1 year prior to first study dose administration
8. Decreased cardiac function with NYHA > Class 2
9. Uncontrolled or significant heart disorder such as unstable angina
10. Significant abnormalities on ECG at Screening. QTcF >450 msec for males or >470 msec for females at Screening
11. Contraindications to MRI and use of intravenous gadolinium-based contrast agents
12. History of severe allergic, anaphylactic, or other infusion related reaction to a previous biologic agent
13. Treatment with any anticancer therapy or participation in another therapeutic clinical study with investigational drugs = 28 days prior to first dose of cabiralizumab
14. Known history of ADAs to previous biologic agents
15. Known history of sensitivity to any component of the study drug formulation
16. Consumption of non-pasteurized milk on a regular basis, or known significant risk of exposure to opportunistic intracellular infections such as listeria, or other such pathogens.
17. Receipt of any vaccine within 28 days prior to first day of treatment. The effect of cabiralizumab on mounting an immunologic vaccine response is not known. Flu or other vaccinations may be administered while on study but the impact of cabiralizumab on the safety and efficacy of the vaccination is unknown.
18. Current unresolved infection or history of chronic active clinically significant infection (viral [e.g., HBV, HCV], bacterial, fungal, or other), which in the opinion of the Investigator would place the patient at risk from exposure to a CSF1R inhibitor
19. Known positive test for human immunodeficiency virus (HIV)
20. Active TB
21. Positive test for latent TB at Screening (T-spot or Quantiferon test)
22. History of prior malignancy, except:
• Curatively treated non-melanoma skin malignancy
• Cervical cancer in situ
• Solid tumor treated curatively more than 2 years previously without evidence of recurrence
23. Lack of peripheral venous access or any condition that would interfere with drug administration or collection of study samples
24. Any uncontrolled medical condition or psychiatric disorder which in the opinion of the Investigator would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results
25. Inability to perform and/or comply with study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method