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Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

This study has been terminated.
(Decision by company to cease development of dovitinib)
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Georgetown University Identifier:
First received: November 30, 2011
Last updated: August 1, 2016
Last verified: November 2015

This study is for women with confirmed hormone receptor positive HER-2 negative advanced breast cancer with evidence of disease resistance to an aromatase inhibitor.

The purpose of this study is to determine how well these medications work together and/or if they have any side effects in patients with hormone-receptor positive metastatic breast cancer who have demonstrated progression of disease after first line hormonal therapy.

This research is being done to determine if taking an already approved medicine (aromatase inhibitor) in combination with a new medication (dovitinib) results in better outcomes for patients with this disease.

Both dovitinib and an aromatase inhibitor are pills that will be taken at home.

Condition Intervention Phase
Breast Cancer
Drug: Dovitinib
Drug: Aromatase Inhibitors
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of TKI258 (Dovitinib) in Combination With an Aromatase Inhibitor in Patients With Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Clinical Benefit Rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Complete response, partial response, or stable disease at 24 weeks from trial entry as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, 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; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

Secondary Outcome Measures:
  • Recommended Phase 2 Dose [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    The dose of dovitinib at which 1 or less subjects experience a dose limiting toxicity when administered every day for 5 days followed by 2 days off schedule in combination with an aromatase inhibitor

  • Number of Participants With Adverse Events [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Number of participants experiencing adverse events

  • Pharmacodynamic Effects [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Expression of pFGFR, pFRS2, pERK in tumor tissue and VEGF, bFGF, PLGF, sVEGFR1/2 and FGF23 levels in plasma

  • Progression-free Survival [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Length of time from study entry until progressive disease

Enrollment: 12
Study Start Date: April 2012
Estimated Study Completion Date: December 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dovitinib plus aromatase inhibitors
Dovitinib with aromatase inhibitor
Drug: Dovitinib
Dovitinib at the recommended Phase 2 dose for 5 consecutive days followed by a 2-day rest
Other Name: TKI258
Drug: Aromatase Inhibitors
Patients will receive one of the aromatase inhibitors either anastrozole 1 mg po daily, letrozole 2.5 mg po daily, or exemestane 25 mg po daily
Other Names:
  • Arimidex
  • Femara
  • Aromasin

Detailed Description:
This is a Phase I/Phase II open-label single arm trial of dovitinib in combination with anastrozole 1 mg daily, exemestane 25 mg daily, or letrozole 2.5 mg daily. Study subjects will receive the aromatase inhibitor on which they had previously derived clinical benefit.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female patients with breast cancer either in the primary or metastatic setting
  • Tumor must be estrogen receptor and/or progesterone receptor positive and Her-2 negative
  • Evidence of disease resistance to an aromatase inhibitor
  • ECOG performance status 0 or 1
  • Age 18 years or older
  • Adequate laboratory values
  • Able to give written informed consent
  • Measurable disease
  • No more than 2 prior chemotherapy regimens in the metastatic setting
  • Unlimited prior hormonal therapy in the metastatic setting
  • Life expectancy of greater than 3 months
  • Post-menopausal
  • Tumor must be available for central testing for FGFR1 amplification by FISH/CISH

Exclusion Criteria:

  • Brain metastases
  • Another primary malignancy within 3 years prior to starting drug therapy with the exception of adequately treated in-site carcinoma of the uterine cervix or skin cancer
  • Chemotherapy within 3 weeks prior to starting study drug or not recovered from side effects of previous therapy
  • Administration of nitrosurea or mitomycin-C within 6 weeks prior to starting study drug or not recovered from side effects of such therapy
  • Administration of biologic therapy within 6 weeks prior to starting study drug or not recovered from side effects of such therapy
  • Radiotherapy within 4 weeks prior to starting study drug or 2 weeks in the case of localized radiotherapy or not recovered from radiotherapy toxicities
  • major surgery, open biopsy or significant traumatic injury within 4 weeks prior to starting study drug or a minor procedure, percutaneous biopsy or placement of a vascular access device within 1 week prior to starting study drug or not recovered from side effects of such procedure or injury
  • Chronic concomitant bisphosphonate therapy for the prevention of bone metastases. Bisphosphonate/ denosumab therapy for the management of bone metastases or for the treatment of osteoporosis s allowed.
  • Impaired cardiac function or clinically significant cardiac disease
  • Impairment of GI function or GI disease that may significantly alter the absorption of dovitinib
  • Cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
  • Known diagnosis of HIV infection
  • Anticoagulation treatment with therapeutic doses of warfarin
  • Any concurrent severe and/or uncontrolled concomitant medical condition that could cause unacceptable safety risks or compromise compliance with the protocol
  • Pregnant or breast-feeding
  • Unwilling or unable to comply with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01484041

United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
Novartis Pharmaceuticals
Principal Investigator: Claudine Isaacs, MD Georgetown University
  More Information

Responsible Party: Georgetown University Identifier: NCT01484041     History of Changes
Other Study ID Numbers: LCCC 2010-535 
Study First Received: November 30, 2011
Results First Received: March 10, 2016
Last Updated: August 1, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No
Plan Description: Will not be reporting outcome data as study closed by sponsor prior to completing accrual. Will be reporting aggregate findings for correlative science project

Keywords provided by Georgetown University:
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on October 21, 2016