Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Hormones

Fulvestrant

Dasatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Tyrosine

Group 2 will receive Fulvestrant and Dasatinib.

Group 3 will receive Fulvestrant and MK-0646.

Group 4 will receive Fulvestrant, MK-0646, and Dasatinib.

Starting dose of 500 mg through a needle into muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. On Day 1 of Cycle 1, injections into 2 different muscles, all other times one injection.

Group 3 or Group 4, receive starting dose of 5 mg/kg by vein on Days 1, 18, 15, and 22 of every cycle.

MK-0646

Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.

Ana Gonzalez-Angulo, MD, MS

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.

The Study Drugs:

Fulvestrant is designed to block estrogen from helping breast cancer tumor cells grow. By blocking estrogen, it may stop tumor growth.

Dasatinib is designed to change the function of genes. By changing the function of these genes, it may prevent cancer from growing and spreading.

MK-0646 is designed to block proteins that help breast cancer cells grow. By blocking these proteins, it may cause the cancer cells to die.

Study Procedures:

You will have a fine needle aspiration or core needle biopsy before you start the study treatment and after 2 weeks. These biopsies are to study genes and proteins, and to see how they change with treatment.

Study Groups:

If you are found to be eligible to take part in this study: you will be enrolled in Phase I or Phase II of the study, depending on when you join the study.

If you are in Phase I, you will be assigned to either Group 1, 2, 3, or 4. If you are in Phase II, (based on the result of the screening biopsy) you will be randomly assigned (as in a roll of dice) to either Group 1, 2, 3, or 4:

* Group 1 will receive fulvestrant only.
* Group 2 will receive fulvestrant and dasatinib.
* Group 3 will receive fulvestrant and MK-0646.
* Group 4 will receive fulvestrant, MK-0646, and dasatinib.

All participants will receive the same dose level of fulvestrant.

If you are in Groups 2, 3, or 4, the dose of MK-0646 and/or dasatinib you receive will depend on when you joined this study. The first set of participants in each group will receive the lowest dose level of MK-0646 and/or dasatinib. Each new set will receive a higher dose of MK-0646 and/or dasatinib than the set before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of MK-0646 and/or dasatinib is found. This is called the Phase I portion of the study.

If you are enrolled in the Phase II portion of the study, you will receive dasatinib at the dose that was tolerated in the Phase I portion.

Study Drug Administration:

Every 28 days makes up 1 study cycle.

You will receive fulvestrant through a needle into your muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. You will have 2 injections each time into 2 different muscles.

If you are in Group 3 or Group 4, you will receive MK-0646 through a needle in your vein weekly.

If you are in Group 2 or Group 4, you will take capsules of dasatinib by mouth every day while you are on study. You should take the drug at about the same time each day with a cup (8 ounces) of water. The study staff will give you a card on which you must record every time that you take dasatinib.

Study Visits:

On Day 1 of every cycle for the first 4 cycles, and then every 3 cycles, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your weight.
* Your performance status will be recorded.
* You will be asked about any other drugs you may be taking.
* Blood (about 1 tablespoon) will be drawn for routine tests and to see how your immune system may be responding to the study drug.

On Day 1 of each cycle, the following procedure will be performed:

-You will be asked about any side effects you may be having.

On Day 1 of Cycle 1, your vital signs will be measured.

On Days 8 and 22 of Cycle 1, your vital signs and weight will be measured. You will have an ECG.

On Day 15 of Cycle 1, the following tests and procedures will be performed:

* Your vital signs and weight will be measured.
* You will have an ECG.
* You will have a PET scan
* You will have a core needle biopsy (which removes more tissue) and/or a fine needle aspiration (which has a smaller needle).

On Days 1, 8, 15, and 22 of Cycles 2 and beyond, your weight will be measured.

On Day 1 of Cycle 4 and every 3 cycles after that, you will have CT scans of the chest, abdomen and/or pelvis, to check the status of the disease. If the disease has spread, you may also have a bone scan and/or x-rays of the bones.

If you are taking warfarin to prevent abnormal blood clotting, blood (about 1-2 teaspoons) will be drawn to check your blood clotting function at least 1 time a week until your blood clotting function becomes stable. After that, blood (about 1-2 teaspoons) will continue being drawn to check your blood clotting function as often as the doctor decides is needed.

Length of Study:

You may receive the study therapy until either you experience intolerable side effects or if the disease gets worse; then you will be taken off study.

End-of-Study Visit:

After you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* You will be asked about any other drugs you may be taking and about any side effects you may be having.
* Your performance status will be recorded.
* Blood (about 2 teaspoons) will be collected for routine tests.
* You will have a hearing test if you received MK-0646.

Four (4), 8, and 12 weeks after the last dose of study drug, blood (about 1 tablespoon) will be drawn to see how your immune system may have responded to the study drug.

This is an investigational study. MK-0646 is not FDA-approved or commercially available. At this time, MK-0646 is only being used in research. Fulvestrant is currently FDA -approved and commercially available for the treatment of metastatic breast cancer in post-menopausal women. Dasatinib is FDA-approved and commercially available to treat chronic myeloid leukemia. At this time, the use of dasatinib in breast cancer patients is investigational.

Up to 40 patients will take part in this study at University of Texas (UT) MD Anderson Cancer Center.

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

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

Maximum Tolerated Dose (MTD) defined as the dose or dose-combination that has the mean posterior toxicity rate closest to the target toxicity rate of 0.33. Dose levels reviewed with each 28 day cycle. Treatment dose levels:

Fulvestrant will be given using a loading dose of 500 mg intramuscularly (IM) on day 1 as two 250 mg/5 ml injections, followed by 500 mg IM on day 15 and on day 1 of each subsequent 28- day (+/- 2 days) cycle.

MK-0646 will be given intravenously on days 1,8, 15, and 22 for each cycle at one of the two dose levels: 1) 5 mg/kg or 2) 10 mg/kg (Dose level 1)

Dasatinib will be given orally (PO) continuously on days 1 -28 for each cycle at one of two dose levels: 1) 70 mg po daily or 2) 100 mg po daily

Bristol-Myers Squibb

Merck Sharp & Dohme LLC

Commonwealth Foundation for Cancer Research

M.D. Anderson Cancer Center

Group 1 will receive Fulvestrant only.

Fulvestrant: Starting dose of 500 mg through a needle into muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. On Day 1 of Cycle 1, injections into 2 different muscles, all other times one injection.

Group 1: Fulvestrant

Group 2 will receive Fulvestrant and Dasatinib.

Fulvestrant: Starting dose of 500 mg through a needle into muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. On Day 1 of Cycle 1, injections into 2 different muscles, all other times one injection.

Dasatinib: Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.

Group 2: Fulvestrant + Dasatinib

Group 3 will receive Fulvestrant and MK-0646.

Fulvestrant: Starting dose of 500 mg through a needle into muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. On Day 1 of Cycle 1, injections into 2 different muscles, all other times one injection.

MK-0646: Group 3 or Group 4, receive starting dose of 5 mg/kg by vein on Days 1, 18, 15, and 22 of every cycle.

Group 3: Fulvestrant + MK-0646

Group 4 will receive Fulvestrant, MK-0646, and Dasatinib.

Fulvestrant: Starting dose of 500 mg through a needle into muscle on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 and beyond. On Day 1 of Cycle 1, injections into 2 different muscles, all other times one injection.

MK-0646: Group 3 or Group 4, receive starting dose of 5 mg/kg by vein on Days 1, 18, 15, and 22 of every cycle.

Dasatinib: Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.

Group 4: Fulvestrant, MK-0646 + Dasatinib

Total

<=18 years

Between 18 and 65 years

>=65 years

Age, Categorical

Age, Continuous

Female

Male

Gender

Hispanic or Latino

Not Hispanic or Latino

Unknown or Not Reported

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Race (NIH/OMB)

United States

Region of Enrollment

Study terminated early due to small sample size.

Ana Gonzalez-Angulo, MD / Associate Professor, Breast Medical Oncology

Study terminated early; Analysis not available due to smaller sample size.

Phase I Maximum Tolerated Dose (MTD) for Dose Level 1

Patient Response (+ Time to Disease Progression)

Overall Study

Symptoms and General Pathology

Behaviors and Mental Disorders

Hot Flashes

Quality of Life

A 2 to 4 weeks run-in period is planned, during which all patients receive single blinded "hot flash evaluation treatment" which is actually a placebo (2 tablets every morning and every evening during 2 to 4 weeks). At the end of this period, the hot flash score is calculated. If the score is ≥10, the patient can be randomized to one of the 2 arms:

* Experimental: BRN01
* Placebo Comparator: Placebo

2 tablets every morning and every evening during 8 to 10 weeks. Each patient will receive 1 set of 5 treatment boxes (60 tablets/box).

BRN01

Placebo

Pierre Etienne Heudel, MD

The purpose of this study is to evaluate the efficacy of a homeopathic treatment (BRN01) in reducing hot flash scores after 4 weeks of treatment.

Chemotherapy is used as an adjuvant treatment for breast cancer, like hormone therapy in patients with hormone-sensitive breast cancer or immunotherapy in those with Human Epidermal growth factor Receptor 2 (HER2)-overexpressing cancer.

These adjuvant treatments reduce the risk of recurrence and metastasis. The side effects of hormone therapy are known and depend on the therapeutic strategy and the drugs used. The side effects of Tamoxifen are similar to menopausal symptoms: hot flashes (half of the female population), vaginal dryness or leukorrhea, nausea, irregular menstruation, benign ovarian cyst and, less frequently, weight gain. Aromatase inhibitors have the same side effects, though with lesser frequency and intensity. The incidence rate of hot flashes after adjuvant treatment in menopausal women with localized breast cancer is 60 to 65 %, and these reactions are very severe in one third of these women. Despite this fact, the management of hot flashes is not systematic and there is currently no therapeutic strategy with proven efficiency. BRN01 (Boiron laboratory) is a homeopathic remedy whose active ingredient is already present in other homeopathic drugs indicated for the management of menopausal hot flashes. BRN01 could reduce the intensity of the reaction in women with breast cancer receiving adjuvant hormonal treatment.

Evaluation of Homeopathic Treatment for Hot Flashes in Non Metastatic Breast Cancer

Placebo-controlled Evaluation of the Homeopathic Drug BRN01 for the Treatment of Hot Flashes in Women With Non Metastatic Breast Cancer Treated by Adjuvant Hormonal Therapy

The hot flash score is equal to: (number of hot flashes/day) x (mean intensity/day).

Treatment efficiency scores will be calculated as follows: (hot flash score on the 4th week of the second period)-(hot flash score on the 2nd week of the first period).

Then efficiency scores will be compared between the 2 arms (placebo versus BRN01).

Treatment efficacy scores will be calculated as follows: (hot flash score on the 8th week of the second period)-(hot flash score on the 2nd week of the first period).

Then efficiency scores will be compared between the 2 arms (placebo versus BRN01).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer	NCT00903006	Breast Cancer	Fulvestrant MK-0646 Dasatinib	18 Years -	M.D. Anderson Cancer Center
Evaluation of Homeopathic Treatment for Hot Flashes in Non Metastatic Breast Cancer	NCT01246427	Breast Cancer	BRN01 Placebo	18 Years -	Centre Leon Berard
Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer	NCT00903006	Breast Cancer	Fulvestrant MK-0646 Dasatinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for adjuvant hormonal therapy