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

Sponsor
Andrew J. Wagner, MD, PhD (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01207492
Collaborator
Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other), Novartis (Industry)
17
Enrollment
7
Locations
1
Arm
147
Anticipated Duration (Months)
2.4
Patients Per Site
0
Patients Per Site Per Month

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.

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 Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 1, 2010
Actual Primary Completion Date :
Apr 1, 2014
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nilotinib

Nilotinib 200 mg taken as 400 mg twice daily, continuously

Drug: nilotinib
Taken orally twice daily

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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

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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Sarcoma Oncology CenterSanta MonicaCaliforniaUnited States90403
2Stanford University Medical CenterStanfordCaliforniaUnited States94305
3H. Lee Moffitt Cancer CenterTampaFloridaUnited States33612
4Massachusetts General HospitalBostonMassachusettsUnited States02114
5Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215
6Fox Chase Cancer CenterPhiladelphiaPennsylvaniaUnited States19111
7UT MD Anderson Cancer CenterHoustonTexasUnited States77030

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.
Responsible Party:
Andrew J. Wagner, MD, PhD, Sponsor, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01207492
Other Study ID Numbers:
  • 10-179
  • YUS23T
First Posted:
Sep 23, 2010
Last Update Posted:
Feb 4, 2022
Last Verified:
Jan 1, 2022
Keywords provided by Andrew J. Wagner, MD, PhD, Sponsor, Dana-Farber Cancer Institute
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleNilotinib
Arm/Group DescriptionNilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily
Period Title: Overall Study
STARTED17
COMPLETED2
NOT COMPLETED15

Baseline Characteristics

Arm/Group TitleNilotinib
Arm/Group DescriptionNilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily
Overall Participants17
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

1. Primary Outcome
TitlePercentage of Participants With Progression Free Survival
DescriptionTo 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 Frame6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleNilotinib
Arm/Group DescriptionNilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily
Measure Participants17
Number (95% Confidence Interval) [percentage of participants with PFS]
82
482.4%
2. Secondary Outcome
TitleOverall Tumor Response Rate (OR)
DescriptionTo 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 Frame2 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleNilotinib
Arm/Group DescriptionNilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily
Measure Participants17
Number (95% Confidence Interval) [percentage of participants]
0
0%
3. Secondary Outcome
TitleClinical Benefit Rate
DescriptionTo 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 Frame6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleNilotinib
Arm/Group DescriptionNilotinib 200 mg taken as 400 mg twice daily, continuously nilotinib: Taken orally twice daily
Measure Participants17
Number (95% Confidence Interval) [percentage of participants]
47
276.5%

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group TitleNilotinib
Arm/Group DescriptionNilotinib 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
Total2/17 (11.8%)
General disorders
Fatigue2/17 (11.8%)
Investigations
Electrocardiogram QT corrected interval prolonged1/17 (5.9%)
Metabolism and nutrition disorders
Hypophosphatemia1/17 (5.9%)
Skin and subcutaneous tissue disorders
Rash maculo-papular1/17 (5.9%)
Other (Not Including Serious) Adverse Events
Nilotinib
Affected / at Risk (%)# Events
Total17/17 (100%)
Blood and lymphatic system disorders
Anemia3/17 (17.6%)
Cardiac disorders
Chest pain - cardiac1/17 (5.9%)
Eye disorders
Scleral disorder1/17 (5.9%)
Eye disorders - Other, specify3/17 (17.6%)
Gastrointestinal disorders
Gastroesophageal reflux disease2/17 (11.8%)
Abdominal pain2/17 (11.8%)
Constipation5/17 (29.4%)
Diarrhea3/17 (17.6%)
Dyspepsia1/17 (5.9%)
Nausea9/17 (52.9%)
Vomiting4/17 (23.5%)
General disorders
Edema face1/17 (5.9%)
Fatigue8/17 (47.1%)
Fever1/17 (5.9%)
Non-cardiac chest pain2/17 (11.8%)
Pain2/17 (11.8%)
Infections and infestations
Lung infection1/17 (5.9%)
Upper respiratory infection4/17 (23.5%)
Investigations
Alanine aminotransferase increased5/17 (29.4%)
Aspartate aminotransferase increased5/17 (29.4%)
Blood bilirubin increased2/17 (11.8%)
Lipase increased1/17 (5.9%)
Platelet count decreased1/17 (5.9%)
Weight loss2/17 (11.8%)
Metabolism and nutrition disorders
Anorexia3/17 (17.6%)
Hyperkalemia1/17 (5.9%)
Hypocalcemia2/17 (11.8%)
Hypomagnesemia1/17 (5.9%)
Hyponatremia1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia2/17 (11.8%)
Back pain1/17 (5.9%)
Bone pain2/17 (11.8%)
Myalgia4/17 (23.5%)
Musculoskeletal and connective tissue disorder - Other, specify3/17 (17.6%)
Nervous system disorders
Dizziness2/17 (11.8%)
Headache7/17 (41.2%)
Peripheral sensory neuropathy1/17 (5.9%)
Psychiatric disorders
Restlessness1/17 (5.9%)
Insomnia2/17 (11.8%)
Renal and urinary disorders
Urinary frequency2/17 (11.8%)
Reproductive system and breast disorders
Vaginal dryness1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Hoarseness1/17 (5.9%)
Sore throat1/17 (5.9%)
Cough1/17 (5.9%)
Dyspnea2/17 (11.8%)
Pleural effusion1/17 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia3/17 (17.6%)
Dry skin4/17 (23.5%)
Hyperhidrosis1/17 (5.9%)
Pruritus2/17 (11.8%)
Rash acneiform4/17 (23.5%)
Rash maculo-papular9/17 (52.9%)
Vascular disorders
Hypertension1/17 (5.9%)

Limitations/Caveats

[Not Specified]

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/TitleAndrew Wagner, MD, PhD
OrganizationDana-Farber Cancer Institute
Phone617.632.5204
Emailandrew_wagner@dfci.harvard.edu
Responsible Party:
Andrew J. Wagner, MD, PhD, Sponsor, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01207492
Other Study ID Numbers:
  • 10-179
  • YUS23T
First Posted:
Sep 23, 2010
Last Update Posted:
Feb 4, 2022
Last Verified:
Jan 1, 2022