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Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dovitinib

Aromatase Inhibitors

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast cancer, postmenopausal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Georgetown Lombardi Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dovitinib plus aromatase inhibitors

Arm Description

Dovitinib with aromatase inhibitor

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Number of Participants With Adverse Events

Number of participants experiencing adverse events

Pharmacodynamic Effects

Expression of pFGFR, pFRS2, pERK in tumor tissue and VEGF, bFGF, PLGF, sVEGFR1/2 and FGF23 levels in plasma

Progression-free Survival

Length of time from study entry until progressive disease

Full Information

NCT ID

NCT01484041

First Posted

November 30, 2011

Last Updated

January 15, 2018

Sponsor

Georgetown University

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01484041

Brief Title

Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Terminated

Why Stopped

Decision by company to cease development of dovitinib

Study Start Date

April 2012 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Georgetown University

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast cancer, postmenopausal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dovitinib plus aromatase inhibitors

Arm Type

Experimental

Arm Description

Dovitinib with aromatase inhibitor

Intervention Type

Drug

Intervention Name(s)

Dovitinib

Other Intervention Name(s)

TKI258

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Aromatase Inhibitors

Other Intervention Name(s)

Arimidex, Femara, Aromasin

Intervention Description

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

Primary Outcome Measure Information:

Title

Clinical Benefit Rate

Description

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Recommended Phase 2 Dose

Description

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

Time Frame

4 weeks

Title

Number of Participants With Adverse Events

Description

Number of participants experiencing adverse events

Time Frame

24 weeks

Title

Pharmacodynamic Effects

Description

Expression of pFGFR, pFRS2, pERK in tumor tissue and VEGF, bFGF, PLGF, sVEGFR1/2 and FGF23 levels in plasma

Time Frame

24 weeks

Title

Progression-free Survival

Description

Length of time from study entry until progressive disease

Time Frame

24 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Claudine Isaacs, MD

Organizational Affiliation

Georgetown University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Georgetown Lombardi Comprehensive Cancer Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing 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

Learn more about this trial

Dovitinib Plus an Aromatase Inhibitor for Metastatic Breast Cancer

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