Clinical trial NCT01207492: Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor
Official title: A Multi-Center Single Agent Phase II Study of the Efficacy of Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pigmented Villonodular Synovitis
Diffuse-type Giant Cell Tumor
Tenosynovial Giant Cell Tumor
Keywords: nilotinib
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: Novartis
First posted: 2010-09-23
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Nilotinib is a drug that is used to treat a form of a blood cancer called leukemia. Nilotinib works by blocking the action of a protein that might be important for the growth of pigmented villonodular synovitis (PVNS). In this research study the investigators are testing whether nilotinib can stop the growth of PVNS or improve the symptoms experienced from PVNS.

Detailed description: * In this research study, each cycle of study drug dosing will last 4 weeks (28 days). During each cycle, participants will take nilotinib by mouth twice daily. During the first cycle, participants will come to the clinic on Days 1 and 8. For Cycles 2-4 and every 3 cycles thereafter, they will come to the clinic on Day 1.
* The following tests and procedures will be performed at specific time points during study treatment: MRI or CT scans; physical examinations; vital signs; blood work; questionnaires and EKG.
* Participants may continue in this research study for as long as they do not have serious side effects or their disease does not get worse.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of recurrent PVNS ( or diffuse-type giant cell tumor or tenosynovial giant cell tumor) that is unresectable, metastatic, or for which the patient refuses surgical intervention
* Progressive disease in the last 12 months, as demonstrated by imaging or clinical appearance of new tumors, in the opinion of the treating investigator
* At least one site of measurable disease according to RECIST 1.1 on MRI (or CT scan for metastatic disease)
* Any number or type of prior systemic therapies, with the exception of known or suspected CSF1 receptor inhibitors as outlined in exclusion criteria below
* 18 years of age or older
* Life expectancy greater than 6 months
* ECOG Performance Status of 0, 1 or 2
* Normal organ and marrow function as defined in the protocol
* QTc less than or equal to 450 ms on 12-lead ECG
* Negative urine or serum pregnancy test within days of start of study drug administration for women of childbearing potential.
* Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following study drug discontinuation

Exclusion Criteria:

* Prior treatment with known or suspected CSF1 receptor inhibitor, including nilotinib, imatinib, sunitinib, or sorafenib, or other approved or investigational tyrosine kinase inhibitors used for treatment of diffuse-type giant cell tumor
* Concurrent treatment with other investigational agents
* Inability to tolerate or contraindication to MRI scanning for participants with localized disease
* Impaired cardiac function
* Current treatment with strong CYP3A4 inhibitors that cannot either be discontinued or switched to a different medication prior to starting study drug
* Current treatment with any medications that have the potential to prolong the QT interval and that cannot either be discontinued or switched to a different medication prior to starting study drug
* Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
* Acute or chronic pancreatic disease
* Acute or chronic liver disease
* Another primary malignant disease requiring systemic treatment or radiation
* History of significant congenital or acquired bleeding disorder unrelated to cancer
* Major surgery within 28 days prior to Day 1 of the study
* Treatment with other investigational agents within 28 days of day 1
* History of non-compliance to medical regimens or inability to grant consent
* Women who are pregnant or breastfeeding
* Other comorbidities that would interfere with study participation or safety in the opinion of the investigator

Primary outcomes:
measure: Percentage of Participants With Progression Free Survival
timeFrame: 6 months
Secondary outcomes:
measure: Overall Tumor Response Rate (OR)
timeFrame: 2 years
measure: Clinical Benefit Rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Andrew J. Wagner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: