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Personalized Treatment Selection for Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Personalized Treatment Selection for Metastatic Breast Cancer

The Study Drug:

Dasatinib blocks several different enzymes called protein kinases that are found in cancer
cells. These enzymes are important to cancer cell growth. Blocking these kinases may stop
or slow cancer growth.

AZD6244 is designed to block the growth of cancer cells by interfering with specific
targeted molecules needed for tumor growth, rather than by simply interfering with rapidly
dividing cells (like in traditional chemotherapy).

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take either dasatinib
or AZD6244. The drug you take will be decided by your doctor based on the findings of the
tumor biopsy.

If you take dasatinib, you will take 2 dasatinib tablets by mouth once every day. The
dasatinib tablets will need to be swallowed whole and can be taken with or without a meal.

If you take AZD6244, you will take 3 tablets by mouth twice every day. The AZD6244 tablet
will need to be taken with 8 ounces of water on an empty stomach (1 hour before or 2 hours
after a meal) about 12 hours apart.

If you have side effects, the study doctor may decrease your dose or you may stop receiving
the study drug for up to 21 days.

While you receive treatment with dasatinib or AZD6244, you may not receive other anti-cancer
treatment such as chemotherapy or hormonal therapy.

If you are receiving treatment with a bisphosphonate that is given by vein (such as Aredia
or Zometa), you will not be able to receive the drug during the first 8 weeks of this study.
This is done in order to avoid low calcium levels in the blood. You may be able to continue
to receive the study drug after the first 8 weeks.

Study Visits:

Every 4 weeks while on study, you will have a complete physical exam. Blood (about 3-4
teaspoons) will be drawn for routine tests.

If you are taking dasatinib, at Week 4, you will have an ECG.

If you are taking AZD6244, at Week 8, and experience heart-related side effects suggestive
of cardiac problems, you will have an ECHO or MUGA.

Every 8 weeks, the scans (such as MRIs, CTs, and bone scans) and x-rays that were performed
at screening will be repeated.

If you experience visual disturbances while receiving AZD6244, you will have an eye exam.

Length of Study:

You may continue taking the study drug daily for as long as you are benefitting. You will
be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

If you are taken off study because of side effects, you will have CT scans or x-rays to
check the status of the disease.

This is an investigational study. Dasatinib is FDA approved to treat chronic myeloid
leukemia. It is not yet FDA approved for the treatment of patients with breast cancer. At
this time, the use of dasatinib in breast cancer patients is investigational. AZD6244 is not
FDA approved or commercially available. Its use in this study is investigational.

The tests that will be used to find out if you can receive treatment with dasatinib or
AZD6244 are also investigational.

Up to 769 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. (Turnstile One - Applies only to inclusion criteria 1 - 4): Histologically confirmed
breast cancer and evidence of metastatic disease that can be biopsied with acceptable
risk. Patients must agree to mandatory fine needle aspiration of the cancer for
response marker determination. Patient must have a positive gene expression profile.
Positive gene expression signature obtained separately on trial LAB11-0337 will also
be acceptable for eligibility.

2. Patients must have measurable or evaluable disease as defined by the RECIST criteria.

3. Subject, age > 18 years (the safety and efficacy of dasatinib and the appropriate
dose has not been established for children).

4. Signed written informed consent including a HIPAA form according to institutional

5. (Turnstile Two Applies Only to Inclusion Criteria 5 -17) - Therapy with Dasatinib -
Patient must have a positive gene expression profile. Positive gene expression
obtained separately on trial LAB11-0337 will also be acceptable for eligibility.

6. Performance status Zubrod scale 0-2 (Appendix B) within 8 days of starting therapy.

7. Full physical examination and history including documentation of weight, height, and
vital signs within 8 days of starting therapy.

8. Patients may have received any number of previous therapies for metastatic breast
cancer. Patients must have received, had a contraindication to, or declined treatment
with an anthracycline and taxane (and Herceptin if HER-2 positive) in either the
adjuvant or metastatic setting.

9. Adequate organ function assessed within 14 days of study therapy, defined as:
(a)Total bilirubin Hepatic enzymes (AST, ALT ) Mg2+, Phosphate and Ca2+ >/= lower limit of normal (LLN); (d) Serum Creatinine < 1.5
time the institutional ULN; and (e) Hemoglobin, Neutrophil count, Platelets, PT, PTT
all Grade 0-1.

10. A baseline EKG within 14 days of starting therapy, with a QTc interval not > 460 msec
in women, or > 450 in men.

11. Ability to take oral medication (dasatinib must be swallowed whole).

12. Patient must agree to discontinue St. Johns Wort while receiving dasatinib therapy if
previously taken.

13. Patient must agree that IV bisphosphonate therapy will be withheld for the first 8
weeks of dasatinib therapy due to risk of hypocalcemia. (After the need for Ca2+
supplementation has been assessed and levels documented to be >LLN, subjects on prior
bisphosphonate may be restarted with caution at the investigator's discretion).

14. Females of childbearing potential must have a negative serum pregnancy test within 7
days of starting therapy.

15. Persons of reproductive potential must agree to use and utilize a barrier method of
contraception throughout treatment and for at least 4 weeks after study drug is

16. Concurrent medications must be assessed, and patient must agree to discontinue all
restricted medications within 7 days of starting therapy.

17. Stable brain metastasis for at least 3 months

Exclusion Criteria:

1. (Only turnstile II applies to Exclusion Criteria): Known allergy to study drug.

2. Concurrent medical condition which may increase the risk of toxicity, including: (a)
pleural or pericardial effusion of any grade; (b) uncontrolled angina, congestive
heart failure or MI within (6 months); (c) history of congenital long QT syndrome or
prolonged QTc interval on pre-entry electrocardiogram > 460 msec in women and >450
msec. in men; (d) any history of clinically significant ventricular arrhythmias (such
as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
continued in excl # 3

3. Continued from exclusion # 2: (e) subjects with hypokalemia or hypomagnesemia if it
cannot be corrected prior to dasatinib administration; (f) history of significant
bleeding disorder unrelated to cancer, including diagnosed congenital bleeding
disorders (e.g., von Willebrand's disease) or acquired bleeding disorder within one
year (e.g., acquired anti-factor VIII antibodies); (g) ongoing or recent (3 months)
significant gastrointestinal bleeding

4. Concomitant medications with any of the following drugs should be considered for
exclusion unless discontinued 7 days prior to starting dasatinib: (a) Category I
drugs that prolong QT interval and are generally accepted to have a risk of causing
Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone,
sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine,
haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol,
methadone, arsenic, chloroquine, and domperidone. Cont. in exclusion # 5

5. Continued from exclusion criterion # 4: halofantrine, levomethadyl, pentamidine,
sparfloxacin, lidoflazine.

6. CYP3A4 inhibitors. Dasatinib is primarily metabolized by the CYP3A4 enzyme.
Therefore, potent inhibitors of CYP3A4 may increase dasatinib plasma concentrations:
(i) ketoconazole, itraconazole, erythromycin, clarithromycin,ritonavir, atazanavir,
indinavir, nefazodone, nelfinavir, saquinavir; (ii) telithromycin; and (iii) subjects
should be advised not to consume substantial quantities of grapefruit juice.

7. Medications which durably inhibit platelet function or inhibit anticoagulation.
Medications which directly and durably inhibit platelet function or coagulation
include: (i) aspirin or aspirin-containing combinations, clopidogrel, dipyridamole,
tirofiban, dipyridamole, epoprostenol, eptifibatide, cilostazol, abciximab,
ticlopidine, cilostazol; and (ii) warfarin, heparin/low molecular weight heparin
[e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]. Exceptions: low-dose warfarin
for prophylaxis to prevent catheter thrombosis, and heparin for flushes of IV lines
is allowed.

8. Women who are unwilling or unable to use a barrier method of contraception to avoid
pregnancy for the entire study period and for at least 4 weeks after cessation of
study drug, or have a positive pregnancy test at baseline, or are pregnant or
breast-feeding. Prior to study enrollment, women of childbearing potential must be
advised of the importance of avoiding pregnancy during trial participation and the
potential risk factors for an unintentional pregnancy.

9. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness.

10. Exclusion from Selumetinib therapy include Uncontrolled hypertension (BP >/=150/95
mmHg), Heart failure (NYHA >/= Class II), prior or current cardiomyopathy (LVEF 50%), Atrial fibrillation (heart rate >100 bpm), Unstable ischaemic heart disease (MI
within 6 months prior, or angina requiring use of nitrates more than once weekly).

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical benefit rate (CB = objective tumor response or stable disease > 6 months)

Outcome Time Frame:

Evaluation within 7 days before starting each cycle of therapy (i.e. every 28 days)

Safety Issue:


Principal Investigator

Stacy Moulder, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2009

Completion Date:

Related Keywords:

  • Breast Cancer
  • Dasatinib
  • Metastatic Breast Cancer
  • Sprycel
  • BMS-354825
  • Genetic testing
  • AZD6244
  • Selumetinib
  • Breast Neoplasms



UT MD Anderson Cancer Center Houston, Texas  77030