Breast CancerPhase 1/2NCT00903006
Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer
A Phase 1/2 study testing Fulvestrant, MK-0646 and Dasatinib in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Fulvestrant, MK-0646 and Dasatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to May 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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)
- Age >/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
- Required laboratory values: Absolute neutrophil count (ANC)>/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L; bilirubin </= 1.5 * upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 * ULN; serum creatinine </= 2.0 * ULN
- 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.
Show all 21Show fewer
- Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).
- Patients must have received prior anti-estrogen therapy in the adjuvant setting.
- Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology).
- Patients must consent to biopsies.
- 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.
- Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease)
- Age >/= 18 years
- ECOG performance status of </= 2
- Required Laboratory Values: ANC >/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L, Bilirubin </= 1.5 * ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 * ULN
- Serum creatinine </= 2.0 * ULN
- 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.
- Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).
- Patients must have received prior anti-estrogen therapy in the adjuvant setting.
- Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology).
- Patients must consent to biopsies.
Who cannot join
- 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
- 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).
- Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy.
- 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.
- Active or untreated brain metastasis
- Pleural or pericardial effusion of any grade
Show all 18Show fewer
- Bone only metastases
- Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease).
- Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed).
- 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
- 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).
- Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy.
- 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.
- Active or untreated brain metastasis
- Pleural or pericardial effusion of any grade
- Bone only metastases
- Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease).
- Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Breast Cancer
- Being tested
- Fulvestrant, MK-0646, Dasatinib
- Keywords
- Breast, Hormone receptor-positive metastatic breast cancer, Fulvestrant, Faslodex, MK-0646, Dasatinib, BMS-354825, Sprycel, Adjuvant hormonal therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
Also called Faslodex
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-0646Drug
Group 3 or Group 4, receive starting dose of 5 mg/kg by vein on Days 1, 18, 15, and 22 of every cycle.
DasatinibDrug
Also called BMS-354825, Sprycel
Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Fulvestrant | Active comparator | Group 1 will receive Fulvestrant only. Receives: Drug: Fulvestrant |
| Group 2: Fulvestrant + Dasatinib | Active comparator | Group 2 will receive Fulvestrant and Dasatinib. Receives: Drug: Fulvestrant; Drug: Dasatinib |
| Group 3: Fulvestrant + MK-0646 | Active comparator | Group 3 will receive Fulvestrant and MK-0646. Receives: Drug: Fulvestrant; Drug: MK-0646 |
| Group 4: Fulvestrant, MK-0646 + Dasatinib | Active comparator | Group 4 will receive Fulvestrant, MK-0646, and Dasatinib. Receives: Drug: Fulvestrant; Drug: MK-0646; Drug: Dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I Maximum Tolerated Dose (MTD) for Dose Level 1
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
Measured: 28 day cycle
Patient Response (+ Time to Disease Progression)
Measured: Baseline, after two 28 day cycles, until disease progression.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2009 (estimated)
- Study startNov 2009
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Merck Sharp & Dohme LLC, Commonwealth Foundation for Cancer Research
- Responsible party
- Sponsor
- Investigators
- Ana Gonzalez-Angulo, MD, MS, Study chair, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00903006
- Sponsor's protocol ID
- 2008-0336
- Status last verified
- Jun 2014
- First submitted
- 13 May 2009
- Last updated
- 2 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00903006
- Acronym / sponsor ID
- 2008-0336
- Conditions
- Breast Cancer
- Keywords
- Breast, Hormone receptor-positive metastatic breast cancer, Fulvestrant, Faslodex, MK-0646, Dasatinib, BMS-354825, Sprycel
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 11 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Merck Sharp & Dohme LLC, Commonwealth Foundation for Cancer Research
- Study start
- Nov 2009
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 15 May 2009 (estimated)
- Results
- Posted 2 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: Fulvestrant | Active comparator | Drug: FulvestrantGroup 1 will receive Fulvestrant only. |
| Group 2: Fulvestrant + Dasatinib | Active comparator | Drug: Fulvestrant, Drug: DasatinibGroup 2 will receive Fulvestrant and Dasatinib. |
| Group 3: Fulvestrant + MK-0646 | Active comparator | Drug: Fulvestrant, Drug: MK-0646Group 3 will receive Fulvestrant and MK-0646. |
| Group 4: Fulvestrant, MK-0646 + Dasatinib | Active comparator | Drug: Fulvestrant, Drug: MK-0646, Drug: DasatinibGroup 4 will receive Fulvestrant, MK-0646, and Dasatinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
- 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)
- Age >/= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
- Required laboratory values: Absolute neutrophil count (ANC)>/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L; bilirubin </= 1.5 * upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 * ULN; serum creatinine </= 2.0 * ULN
Key exclusion criteria (18 listed)
- 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
- 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).
- Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy.
- 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.
- Active or untreated brain metastasis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FulvestrantAlso: FaslodexStarting 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. | Drug | Group 1: Fulvestrant, Group 2: Fulvestrant + Dasatinib, Group 3: Fulvestrant + MK-0646, Group 4: Fulvestrant, MK-0646 + Dasatinib |
| MK-0646Group 3 or Group 4, receive starting dose of 5 mg/kg by vein on Days 1, 18, 15, and 22 of every cycle. | Drug | Group 3: Fulvestrant + MK-0646, Group 4: Fulvestrant, MK-0646 + Dasatinib |
| DasatinibAlso: BMS-354825, SprycelGroup 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily. | Drug | Group 2: Fulvestrant + Dasatinib, Group 4: Fulvestrant, MK-0646 + Dasatinib |
Primary outcome
Phase I Maximum Tolerated Dose (MTD) for Dose Level 1
Time frame: 28 day cycle
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
Patient Response (+ Time to Disease Progression)
Time frame: Baseline, after two 28 day cycles, until disease progression.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ana Gonzalez-Angulo, MD, MS study chair
UT MD Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fulvestrant, MK-0646 and Dasatinib in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I Maximum Tolerated Dose (MTD) for Dose Level 1 (time frame: 28 day cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2015.