Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer
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| ClinicalTrials.gov Identifier: NCT00903006 |
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Recruitment Status :
Terminated
(Low Accrual)
First Posted : May 15, 2009
Results First Posted : February 2, 2015
Last Update Posted : February 2, 2015
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Sponsor:
M.D. Anderson Cancer Center
Collaborators:
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Commonwealth Foundation for Cancer Research
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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Brief 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. 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer | Drug: Fulvestrant Drug: MK-0646 Drug: Dasatinib | Phase 1 Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 11 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Study Start Date : | November 2009 |
| Actual Primary Completion Date : | May 2013 |
| Actual Study Completion Date : | May 2013 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Group 1: Fulvestrant
Group 1 will receive Fulvestrant only.
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Drug: 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.
Other Name: Faslodex |
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Active Comparator: Group 2: Fulvestrant + Dasatinib
Group 2 will receive Fulvestrant and Dasatinib.
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Drug: 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.
Other Name: Faslodex Drug: Dasatinib Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.
Other Names:
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Active Comparator: Group 3: Fulvestrant + MK-0646
Group 3 will receive Fulvestrant and MK-0646.
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Drug: 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.
Other Name: Faslodex Drug: 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. |
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Active Comparator: Group 4: Fulvestrant, MK-0646 + Dasatinib
Group 4 will receive Fulvestrant, MK-0646, and Dasatinib.
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Drug: 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.
Other Name: Faslodex Drug: 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. Drug: Dasatinib Group 2 or Group 4, starting dose of 70 mg (capsules) by mouth daily.
Other Names:
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Primary Outcome Measures :
- 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. ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
- 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).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00903006
Locations
| United States, Texas | |
| UT MD Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Commonwealth Foundation for Cancer Research
Investigators
| Study Chair: | Ana Gonzalez-Angulo, MD, MS | UT MD Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00903006 |
| Other Study ID Numbers: |
2008-0336 |
| First Posted: | May 15, 2009 Key Record Dates |
| Results First Posted: | February 2, 2015 |
| Last Update Posted: | February 2, 2015 |
| Last Verified: | June 2014 |
Keywords provided by M.D. Anderson Cancer Center:
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Breast Hormone receptor-positive metastatic breast cancer Fulvestrant Faslodex MK-0646 |
Dasatinib BMS-354825 Sprycel Adjuvant hormonal therapy |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Dasatinib Fulvestrant Antineoplastic Agents Protein Kinase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Hormonal Estrogen Receptor Antagonists Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |