MDACC Study Summary 2008-0336

Study Summary
No. 2008-0336:.......Breast......Ana Gonzalez-Angulo......Breast Medical Oncology

Study Summary Title



Study Summary Number:	2008-0336

Study Title:	A Phase I-II, Randomization, Open-Label Clinical Trial of Fulvestrant Versus the Combination of Fulvestrant, MK-0646, and Dasatinib as Therapy for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer

Physician

New Patient Referral



Name:	Ana Gonzalez-Angulo	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Breast Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2817 Contact us about clinical trials

General Information



Disease Group:	Breast	Supported By:	Bristol Myers Squibb Commonwealth Foundation for Cancer Research Merck

Phase of Study:	Phase I/Phase II	Return Visit:	Patients will be at MDACC for visits on days 1, 8, 15, and 22; then every 3 months.

Treatment Agents:	Dasatinib Faslodex MK-0646	Home Care:	N/A

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goals of this clinical research study are to learn the tolerable and effective doses of the drug Sprycel (dasatinib) in combination with 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.

Study Objectives / Outcomes

Primary Objectives

To determine the tolerability of the combination of fulvestrant or fulvestrant and dasatinib in the Phase I portion of the trial for hormone receptor-positive metastatic breast cancer.
To determine, during the Phase II portion of the trial, if the addition of dasatinib to fulvestrant increases the median progression-free survival in patients with newly diagnosed metastatic hormone receptor-positive, HER2-negative breast cancer
To identify potential predictive (baseline) biomarkers able to determine likelihood of response based on time to progression (TTP)
To identify potential pharmacodynamic (longitudinal) biomarkers (tissue and functional imaging) able to determine likelihood of response based on time to progression (TTP)

Secondary Objectives

To evaluate if the addition of dasatinib to fulvestrant in patients with hormone receptor-positive HER-2-negative breast cancer causes molecular changes (inhibition/activation) in the PI3K and Src pathways and in ER signaling
To evaluate time to progression (TTP) for each treatment group
To evaluate response rates (ORR) for each treatment group
To evaluate the relationship between changes in functional imaging and the molecular changes of PI3K and Src pathways in each treatment group
To assess the toxicity of the treatment regimens

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	11/19/2009

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	100

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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

3) Age >/= 18 years

4) ECOG performance status of </= 2

5) Required laboratory values: ANC>/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L; bilirubin </= 1.5 x ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 x ULN; serum creatinine </= 2.0 x ULN

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 </= 2

15) Required Laboratory Values: ANC >/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L, Bilirubin </= 1.5 x ULN, alanine aminotrasferase (ALT) and aspartate amniotransferase (AST) </= 2.5 x ULN

16) Serum creatinine </= 2.0 xULN

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).

Links

Registration Number: NCT00903006
Study Information on Clinical Trials Registry (clinicaltrials.gov)