Clinical trial NCT01471106: Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer
Official title: Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Estrogen Receptor Negative Breast Cancer
Biomarker studies
Ki-67
Dasatinib
BMS-354825
Sprycel
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Susan G. Komen Breast Cancer Foundation
name: Bristol-Myers Squibb
First posted: 2011-11-11
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this clinical research study is to learn if dasatinib can help prevent breast cancer from developing in the unaffected breast.

Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells.

This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of leukemia. Its use in breast cancer patients in investigational.

Up to 66 patients will take part in this multicenter study. Up to 60 will be enrolled at MD Anderson.

Detailed description: Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 3 study groups:

* If you are in Group 1, you will take dasatinib 40mg once a day by mouth with water.
* If you are in Group 2, you will take dasatinib 80mg once a day by mouth with water.
* If you are in Group 3, you will not receive dasatinib.

You will be given a study drug diary to complete. In the diary, you will record when you take the study drug.

Study Visits:

At Month 1:

* You will be called by a nurse and asked about any drugs you are taking and side effects you may be having.
* You will be asked about any drugs you may be taking and side effects you may be having.
* Your drug diary will be reviewed.

At Month 2 you will be called by a nurse and asked about any drugs you are taking and side effects you may be having. You will also be asked to review your drug diary. This call will take about 20 minutes

At Month 3 (or if you leave the study early):

* You will have a fine needle aspirate (FNA) of the breast for biomarker testing. Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug.
* Blood (about 2-3 tablespoons) will be drawn for biomarker testing.
* You will be asked about any drugs you may be taking and side effects you may be having.
* Your drug diary will be reviewed.

Length of Study:

You may remain on study for up to 3 months. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Eligibility criteria: Inclusion Criteria:

1. Histological confirmation of ER negative breast carcinoma (defined as less than 10%), stage I, II, or III
2. Completed all adjuvant therapy including (if indicated) endocrine, trastuzumab, radiation therapy
3. At least 18 years of age.
4. Female: A female is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation, hysterectomy alone, hysterectomy and bilateral salpingo-oophorectomy, bilateral salpingo-oophorectomy alone or women who are post-menopausal); or b. Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local IRB/IEC: • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm).
5. (Continued from above) • Abstinence from sexual intercourse from 2 weeks prior to administration of the investigational product, throughout the active study treatment period. • Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject. • Any intrauterine device (IUD). • Barrier methods including diaphragm or condom with a spermicide.
6. Able to swallow and retain oral medication.
7. ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
8. Provided written informed consent.
9. Adequate bone marrow function: Hemoglobin \>/= 9 gm/dL. • Absolute granulocyte count \>/= 1,500/mm\^3 (1.5 x 10\^9/L). • Platelets \>/= 75,000/mm\^3 (100 x 10\^9/L).
10. Serum creatinine \< 1.4 mg/dL or calculated creatinine clearance (CrCl) \>/= 30 mL/min
11. Total bilirubin \</= 1.5 times the upper limit of the reference range
12. Aspartate and alanine transaminase (AST or ALT) \</= 2 times the upper limit of the reference range.
13. Patients must have a baseline ECG with QTcF within the normal range within 28 days prior to registration.
14. Normal mammogram of unaffected breast within 12 months prior to study entry.

Exclusion Criteria:

1. Unwillingness to undergo RPFNA.
2. Contraindication to RPFNA including breast implant(s), bilateral radiation, anticoagulation (excluding those on 81mg aspirin).
3. Concurrent medical condition that would increase drug toxicity: Pleural or pericardial effusion, coagulation or platelet function disorder, ongoing or recent (less than 3 months gastrointestinal bleeding)
4. Uncontrolled angina, congestive heart failure, MI (within last 6 months), congenital long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged QTcF interval on pre-entry EKG (greater than normal range)
5. Hypokalemia or hypomagnesemia if it cannot be corrected
6. Is a pregnant or lactating female.
7. Has evidence of recurrent or metastatic (Stage IV) breast cancer.
8. Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
9. Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to dasatinib
10. Has received treatment with any investigational drug in the previous 4 weeks.
11. Has received chemotherapy, immunotherapy, biologic therapy or endocrine therapy within the past 12 weeks.
12. Is currently receiving oral steroid treatment (inhaled steroids are permitted)
13. Oral estrogen, progesterone, testosterone therapy within last 3 months.
14. Concomitant Medications: Drugs that are considered category D (Consider therapy modification) and X (Avoid combination) using the Lexicomp database are prohibited. Concomitant drugs that fall into categories A (No known interaction), B (no action needed) and C (monitor therapy) are allowed.

Primary outcomes:
measure: Change in Ki-67 in Breast Tissue of High-Risk Women
timeFrame: up to 3 months
Secondary outcomes:
measure: To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway
timeFrame: up to 3 months
measure: To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway
timeFrame: up to 3 months
measure: To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway
timeFrame: up to 3 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Banu Arun, MD
role: PRINCIPAL_INVESTIGATOR
References: