Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
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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.
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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.
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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 Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Nilotinib Nilotinib 200 mg taken as 400 mg twice daily, continuously |
Drug: nilotinib
Taken orally twice daily
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Progressive disease in the last 12 months, as demonstrated by imaging or clinical appearance of new tumors, in the opinion of the treating investigator
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At least one site of measurable disease according to RECIST 1.1 on MRI (or CT scan for metastatic disease)
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Any number or type of prior systemic therapies, with the exception of known or suspected CSF1 receptor inhibitors as outlined in exclusion criteria below
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18 years of age or older
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Life expectancy greater than 6 months
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ECOG Performance Status of 0, 1 or 2
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Normal organ and marrow function as defined in the protocol
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QTc less than or equal to 450 ms on 12-lead ECG
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Negative urine or serum pregnancy test within days of start of study drug administration for women of childbearing potential.
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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:
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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
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Concurrent treatment with other investigational agents
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Inability to tolerate or contraindication to MRI scanning for participants with localized disease
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Impaired cardiac function
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Current treatment with strong CYP3A4 inhibitors that cannot either be discontinued or switched to a different medication prior to starting study drug
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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
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Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
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Acute or chronic pancreatic disease
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Acute or chronic liver disease
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Another primary malignant disease requiring systemic treatment or radiation
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History of significant congenital or acquired bleeding disorder unrelated to cancer
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Major surgery within 28 days prior to Day 1 of the study
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Treatment with other investigational agents within 28 days of day 1
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History of non-compliance to medical regimens or inability to grant consent
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Women who are pregnant or breastfeeding
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Other comorbidities that would interfere with study participation or safety in the opinion of the investigator
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Sarcoma Oncology Center | Santa Monica | California | United States | 90403 |
2 | Stanford University Medical Center | Stanford | California | United States | 94305 |
3 | H. Lee Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
4 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
5 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
6 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
7 | UT MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Andrew J. Wagner, MD, PhD
- Brigham and Women's Hospital
- Massachusetts General Hospital
- Novartis
Investigators
- Principal Investigator: Andrew J. Wagner, MD, PhD, Dana-Farber Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 10-179
- YUS23T
Study Results
Participant Flow
Recruitment Details | |
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Pre-assignment Detail |
Arm/Group Title | Nilotinib |
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Arm/Group Description | Nilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily |
Period Title: Overall Study | |
STARTED | 17 |
COMPLETED | 2 |
NOT COMPLETED | 15 |
Baseline Characteristics
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Nilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily |
Overall Participants | 17 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
15
88.2%
|
>=65 years |
2
11.8%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
45.35
(13.54)
|
Sex: Female, Male (Count of Participants) | |
Female |
12
70.6%
|
Male |
5
29.4%
|
Region of Enrollment (participants) [Number] | |
United States |
17
100%
|
Outcome Measures
Title | Percentage of Participants With Progression Free Survival |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
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[Not Specified] |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Nilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily |
Measure Participants | 17 |
Number (95% Confidence Interval) [percentage of participants with PFS] |
82
482.4%
|
Title | Overall Tumor Response Rate (OR) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Nilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily |
Measure Participants | 17 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
Title | Clinical Benefit Rate |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Nilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily |
Measure Participants | 17 |
Number (95% Confidence Interval) [percentage of participants] |
47
276.5%
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Nilotinib | |
Arm/Group Description | Nilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily | |
All Cause Mortality |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 2/17 (11.8%) | |
General disorders | ||
Fatigue | 2/17 (11.8%) | |
Investigations | ||
Electrocardiogram QT corrected interval prolonged | 1/17 (5.9%) | |
Metabolism and nutrition disorders | ||
Hypophosphatemia | 1/17 (5.9%) | |
Skin and subcutaneous tissue disorders | ||
Rash maculo-papular | 1/17 (5.9%) | |
Other (Not Including Serious) Adverse Events |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 17/17 (100%) | |
Blood and lymphatic system disorders | ||
Anemia | 3/17 (17.6%) | |
Cardiac disorders | ||
Chest pain - cardiac | 1/17 (5.9%) | |
Eye disorders | ||
Scleral disorder | 1/17 (5.9%) | |
Eye disorders - Other, specify | 3/17 (17.6%) | |
Gastrointestinal disorders | ||
Gastroesophageal reflux disease | 2/17 (11.8%) | |
Abdominal pain | 2/17 (11.8%) | |
Constipation | 5/17 (29.4%) | |
Diarrhea | 3/17 (17.6%) | |
Dyspepsia | 1/17 (5.9%) | |
Nausea | 9/17 (52.9%) | |
Vomiting | 4/17 (23.5%) | |
General disorders | ||
Edema face | 1/17 (5.9%) | |
Fatigue | 8/17 (47.1%) | |
Fever | 1/17 (5.9%) | |
Non-cardiac chest pain | 2/17 (11.8%) | |
Pain | 2/17 (11.8%) | |
Infections and infestations | ||
Lung infection | 1/17 (5.9%) | |
Upper respiratory infection | 4/17 (23.5%) | |
Investigations | ||
Alanine aminotransferase increased | 5/17 (29.4%) | |
Aspartate aminotransferase increased | 5/17 (29.4%) | |
Blood bilirubin increased | 2/17 (11.8%) | |
Lipase increased | 1/17 (5.9%) | |
Platelet count decreased | 1/17 (5.9%) | |
Weight loss | 2/17 (11.8%) | |
Metabolism and nutrition disorders | ||
Anorexia | 3/17 (17.6%) | |
Hyperkalemia | 1/17 (5.9%) | |
Hypocalcemia | 2/17 (11.8%) | |
Hypomagnesemia | 1/17 (5.9%) | |
Hyponatremia | 1/17 (5.9%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 2/17 (11.8%) | |
Back pain | 1/17 (5.9%) | |
Bone pain | 2/17 (11.8%) | |
Myalgia | 4/17 (23.5%) | |
Musculoskeletal and connective tissue disorder - Other, specify | 3/17 (17.6%) | |
Nervous system disorders | ||
Dizziness | 2/17 (11.8%) | |
Headache | 7/17 (41.2%) | |
Peripheral sensory neuropathy | 1/17 (5.9%) | |
Psychiatric disorders | ||
Restlessness | 1/17 (5.9%) | |
Insomnia | 2/17 (11.8%) | |
Renal and urinary disorders | ||
Urinary frequency | 2/17 (11.8%) | |
Reproductive system and breast disorders | ||
Vaginal dryness | 1/17 (5.9%) | |
Respiratory, thoracic and mediastinal disorders | ||
Hoarseness | 1/17 (5.9%) | |
Sore throat | 1/17 (5.9%) | |
Cough | 1/17 (5.9%) | |
Dyspnea | 2/17 (11.8%) | |
Pleural effusion | 1/17 (5.9%) | |
Skin and subcutaneous tissue disorders | ||
Alopecia | 3/17 (17.6%) | |
Dry skin | 4/17 (23.5%) | |
Hyperhidrosis | 1/17 (5.9%) | |
Pruritus | 2/17 (11.8%) | |
Rash acneiform | 4/17 (23.5%) | |
Rash maculo-papular | 9/17 (52.9%) | |
Vascular disorders | ||
Hypertension | 1/17 (5.9%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Andrew Wagner, MD, PhD |
---|---|
Organization | Dana-Farber Cancer Institute |
Phone | 617.632.5204 |
andrew_wagner@dfci.harvard.edu |
- 10-179
- YUS23T