Overview

Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer

Status:
Terminated

Trial end date:
2013-05-01

Target enrollment:
0

Participant gender:
Female

Summary

The goals of this clinical research study are to learn the tolerable and effective doses of the drug MK-0646 that can be given in combination with Sprycel (dasatinib) and Faslodex (fulvestrant) to patients with hormone receptor-positive metastatic breast cancer. The safety of these drugs will be studied as well as markers in the tumors that may help researchers predict the tumors' reaction to the treatment.

Phase:

Phase 1/Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

M.D. Anderson Cancer Center

Collaborators:

Bristol-Myers Squibb
Commonwealth Foundation for Cancer Research
Merck Sharp & Dohme Corp.

Treatments:

Antibodies, Monoclonal
Dasatinib
Estradiol
Fulvestrant
Hormones

Criteria

Inclusion Criteria:

1. For the Phase I: Patients with histologically or cytologically confirmed diagnosis of
metastatic hormone receptor-positive HER2-negative breast cancer who have received up
to one line of endocrine therapy for metastatic disease.

2. Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) or
evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST
criteria for metastatic disease)

3. Age >/= 18 years

4. Eastern Cooperative Oncology Group (ECOG) performance status of
5. Required laboratory values: Absolute neutrophil count (ANC)>/= 1500 cells/mm^3,
platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L; bilirubin upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate
aminotransferase (AST)
6. Ability to understand the requirements of the study, provided written informed consent
and authorization of use and disclosure of protected health information, and agree to
abide by the study restrictions and to return for the required assessments.

7. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).

8. Patients must have received prior anti-estrogen therapy in the adjuvant setting.

9. Patients may have easily accessible tumors for biopsy (confirmed by interventional
radiology).

10. Patients must consent to biopsies.

11. For the Phase II: Patients with histologically or cytologically confirmed diagnosis of
metastatic hormone receptor-positive, HER2-negative, breast cancer who have received
up to one line of endocrine therapy for metastatic disease.

12. Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions
which do not fulfill RECIST criteria for metastatic disease)

13. Age >/= 18 years

14. ECOG performance status of
15. Required Laboratory Values: ANC >/= 1500 cells/mm^3, platelet count >/= 100,000
cells/mm^3, hemoglobin >/= 9 gm/L, Bilirubin (ALT) and aspartate aminotransferase (AST)
16. Serum creatinine
17. Ability to understand the requirements of the study, provide written informed consent
and authorization of use and disclosure of protected health information, and agree to
abide by the study restrictions and to return for the required assessments.

18. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).

19. Patients must have received prior anti-estrogen therapy in the adjuvant setting.

20. Patients may have easily accessible tumors for biopsy (confirmed by interventional
radiology).

21. Patients must consent to biopsies.

Exclusion Criteria:

1. For the Phase I: History of prior malignancies within the past 5 years with the
exception of curatively treated basal or squamous cell carcinomas of the skin or
carcinoma in situ of the cervix

2. Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes,
hypertension, coronary artery disease, congestive heart failure, ongoing or recent
gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet
function abnormality).

3. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of
starting dasatinib therapy.

4. Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a
fasting serum glucose > 160 mg/dl or hemoglobin A1c > 8% at screening), type 1 or 2
diabetes mellitus.

5. Active or untreated brain metastasis

6. Pleural or pericardial effusion of any grade

7. Bone only metastases

8. Patients for whom endocrine therapy is not appropriate (i.e. life threatening
metastatic disease).

9. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is
allowed).

10. For the Phase II: History of prior malignancies within the past 5 years with the
exception of curatively treated basal or squamous cell carcinomas of the skin or
carcinoma in situ of the cervix

11. Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes,
hypertension, coronary artery disease, congestive heart failure, ongoing or recent
gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet
function abnormality).

12. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of
starting dasatinib therapy.

13. Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a
fasting serum glucose > 160 mg/dl or hemoglobin A1c > 8% at screening), type 1 or 2
diabetes mellitus.

14. Active or untreated brain metastasis

15. Pleural or pericardial effusion of any grade

16. Bone only metastases

17. Patients for whom endocrine therapy is not appropriate (i.e. life threatening
metastatic disease).

18. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is
allowed).