Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

NCT01484041 | Terminated Phase 1 Results DMC

• 1 other identifier: LCCC 2010-535
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Breast cancer; postmenopausal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Recommended Phase 2 Dose

  4 weeks

• Number of Participants With Adverse Events

  24 weeks

• Pharmacodynamic Effects

  24 weeks

• Progression-free Survival

  24 weeks

Study Arms (1)

Dovitinib plus aromatase inhibitors

EXPERIMENTAL

Dovitinib with aromatase inhibitor

Drug: Dovitinib; Drug: Aromatase Inhibitors

Interventions

Dovitinib DRUG

Dovitinib at the recommended Phase 2 dose for 5 consecutive days followed by a 2-day rest

Also known as: TKI258

Dovitinib plus aromatase inhibitors

Aromatase Inhibitors DRUG

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

Also known as: Arimidex, Femara, Aromasin

Dovitinib plus aromatase inhibitors

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Georgetown University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Aromatase Inhibitors; Anastrozole; Letrozole; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Claudine Isaacs
• Organization: Georgetown University

isaacsc@georgetown.edu

2024443677

Study Officials

• Claudine Isaacs, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2011
• First Posted: December 2, 2011
• Study Start: April 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2017
• Last Updated: February 9, 2018
• Results First Posted: September 20, 2016

Record last verified: 2015-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)