Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

A Phase I/II Trial of TKI258 (Dovitinib) in Combination With an Aromatase Inhibitor in Patients With Metastatic Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Dovitinib; Drug: Aromatase Inhibitors

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Lombardi Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 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: Femara; Arimidex; Aromasin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate	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	24 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Claudine Isaacs, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: November 30, 2011
• First Submitted That Met QC Criteria: December 1, 2011
• First Posted (Estimate): December 2, 2011

Study Record Updates

• Last Update Posted (Actual): February 9, 2018
• Last Update Submitted That Met QC Criteria: January 15, 2018
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Breast cancer; postmenopausal
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Aromatase Inhibitors
• Other Study ID Numbers: LCCC 2010-535

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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