Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis; Diffuse-type Giant Cell Tumor
• Intervention / Treatment: Drug: nilotinib

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • UT MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nilotinib; Nilotinib 200 mg taken as 400 mg twice daily, continuously	Drug: nilotinib; Taken orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Progression Free Survival	To estimate progression free survival at 6 months in participants with recurrent PVNS treated with nilotinib. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Tumor Response Rate (OR)	To determine overall tumor response rate [% complete response (CR) + % partial response (PR) by RECIST 1.1]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR) is a disappearance of all target lesions. Partial Response (PR) is a >=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.	2 years
Clinical Benefit Rate	To determine the clinical benefit rate [% CR + % PR + % stable disease by RECIST 1.1] at 6 months. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR) is a disappearance of all target lesions. Partial Response (PR) is a >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	6 months

Collaborators and Investigators

• Sponsor: Andrew J. Wagner, MD, PhD
• Collaborators: Massachusetts General Hospital; Novartis; Brigham and Women's Hospital
• Investigators: Principal Investigator: Andrew J. Wagner, MD, PhD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: September 21, 2010
• First Submitted That Met QC Criteria: September 22, 2010
• First Posted (Estimated): September 23, 2010

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: nilotinib
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Neoplasms; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular
• Other Study ID Numbers: 10-179; YUS23T (Other Identifier: Novartis)