Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

Phase 1

Terminated

Conditions: Breast Cancer

Interventions: Drug: Dovitinib
Drug: Aromatase Inhibitors

Registration Number: NCT01484041

Lead Sponsor: Georgetown University

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 12

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dovitinib plus aromatase inhibitors	Dovitinib	Dovitinib with aromatase inhibitor
Dovitinib plus aromatase inhibitors	Aromatase Inhibitors	Dovitinib with aromatase inhibitor

Primary Outcome Measures

Name	Time	Method
Clinical Benefit Rate	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

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