Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT01484041
• Recruitment Status: Terminated
• First Posted: December 2, 2011
• Results First Posted: September 20, 2016
• Last Update Posted: February 9, 2018
• Sponsor: Georgetown University
• Collaborator: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Georgetown University

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Dovitinib; Drug: Aromatase Inhibitors	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: April 2012
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2017

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Clinical Benefit Rate [ Time Frame: 24 weeks ]
   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 :

1. Recommended Phase 2 Dose [ Time Frame: 4 weeks ]
   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
2. Number of Participants With Adverse Events [ Time Frame: 24 weeks ]
   Number of participants experiencing adverse events
3. Pharmacodynamic Effects [ Time Frame: 24 weeks ]
   Expression of pFGFR, pFRS2, pERK in tumor tissue and VEGF, bFGF, PLGF, sVEGFR1/2 and FGF23 levels in plasma
4. Progression-free Survival [ Time Frame: 24 weeks ]
   Length of time from study entry until progressive disease

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Locations

United States, District of Columbia

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, United States, 20007

Sponsors and Collaborators

Georgetown University

Novartis Pharmaceuticals

Investigators

• Principal Investigator: Claudine Isaacs, MD; Georgetown University

More Information

• Responsible Party: Georgetown University
• ClinicalTrials.gov Identifier: NCT01484041
• Other Study ID Numbers: LCCC 2010-535
• First Posted: December 2, 2011
• Results First Posted: September 20, 2016
• Last Update Posted: February 9, 2018
• Last Verified: November 2015

Individual Participant Data (IPD) Sharing Statement:

• 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; postmenopausal

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; 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