Diffuse-type Giant Cell Tumor, Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor
Conditions
Keywords
nilotinib
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.
Interventions
DRUGnilotinib
Taken orally twice daily
Sponsors
Andrew J. Wagner, MD, PhD
Brigham and Women's Hospital
Massachusetts General Hospital
Novartis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression Free Survival | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response Rate (OR) | 2 years | 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. |
| Clinical Benefit Rate | 6 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAndrew J. Wagner, MD, PhD
Dana-Farber Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nilotinib Nilotinib 200 mg taken as 400 mg twice daily, continuously
nilotinib: Taken orally twice daily | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Nilotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 45.35 years STANDARD_DEVIATION 13.54 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 2 / 17 |
Outcome results
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Percentage of Participants With Progression Free Survival | 82 percentage of participants with PFS |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Clinical Benefit Rate | 47 percentage of participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Overall Tumor Response Rate (OR) | 0 percentage of participants |