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
7
1
153
2.4
0

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 :
Jun 1, 2023

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

  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

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.
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:
Jul 28, 2022
Last Verified:
Jul 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 Title Nilotinib
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

1. Primary Outcome
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
[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%
2. Secondary Outcome
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%
3. Secondary Outcome
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

[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/Title Andrew Wagner, MD, PhD
Organization Dana-Farber Cancer Institute
Phone 617.632.5204
Email andrew_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:
Jul 28, 2022
Last Verified:
Jul 1, 2022