Breast Cancer
Conditions
Keywords
Breast cancer, postmenopausal
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.
Interventions
DRUGDovitinib
Dovitinib at the recommended Phase 2 dose for 5 consecutive days followed by a 2-day rest
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
Sponsors
Novartis Pharmaceuticals
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Pharmacodynamic Effects | 24 weeks | Expression of pFGFR, pFRS2, pERK in tumor tissue and VEGF, bFGF, PLGF, sVEGFR1/2 and FGF23 levels in plasma |
| Progression-free Survival | 24 weeks | Length of time from study entry until progressive disease |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dovitinib Plus Aromatase Inhibitors Dovitinib with aromatase inhibitor
Dovitinib: Dovitinib at the recommended Phase 2 dose for 5 consecutive days followed by a 2-day rest
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 | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Dovitinib Plus Aromatase Inhibitors |
|---|---|
| Age, Continuous | 53.5 years |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 1 / 12 |
Outcome results
Primary
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
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dovitinib Plus Aromatase Inhibitors | Clinical Benefit Rate | 1 participants |
Secondary
Number of Participants With Adverse Events
Number of participants experiencing adverse events
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dovitinib Plus Aromatase Inhibitors | Number of Participants With Adverse Events | 12 participants |
Secondary
Pharmacodynamic Effects
Expression of pFGFR, pFRS2, pERK in tumor tissue and VEGF, bFGF, PLGF, sVEGFR1/2 and FGF23 levels in plasma
Time frame: 24 weeks
Population: Data were not collected for this outcome
Secondary
Progression-free Survival
Length of time from study entry until progressive disease
Time frame: 24 weeks
Population: Data not collected for this outcome as study terminated by company prior to completing accrual
Secondary
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
Time frame: 4 weeks
Population: Subjects on study evaluated for toxicity
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dovitinib Plus Aromatase Inhibitors | Recommended Phase 2 Dose | 400 mg |