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

This study has been terminated.
(Low Accrual)
Sponsor:
Collaborators:
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Commonwealth Foundation for Cancer Research
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00903006
First received: May 13, 2009
Last updated: January 21, 2015
Last verified: June 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: Fulvestrant
Drug: MK-0646
Drug: Dasatinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Phase I Maximum Tolerated Dose (MTD) for Dose Level 1 [ Time Frame: 28 day cycle ] [ Designated as safety issue: Yes ]

    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. ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: November 2009
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: Fulvestrant
Group 1 will receive Fulvestrant only.
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
Active Comparator: Group 2: Fulvestrant + Dasatinib
Group 2 will receive Fulvestrant and Dasatinib.
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:
  • BMS-354825
  • Sprycel
Active Comparator: Group 3: Fulvestrant + MK-0646
Group 3 will receive Fulvestrant and MK-0646.
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.
Active Comparator: Group 4: Fulvestrant, MK-0646 + Dasatinib
Group 4 will receive Fulvestrant, MK-0646, and Dasatinib.
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:
  • BMS-354825
  • Sprycel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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)
  3. Age >/= 18 years
  4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
  5. 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
  6. 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.
  7. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).
  8. Patients must have received prior anti-estrogen therapy in the adjuvant setting.
  9. Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology).
  10. Patients must consent to biopsies.
  11. 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.
  12. Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease)
  13. Age >/= 18 years
  14. ECOG performance status of </= 2
  15. 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
  16. Serum creatinine </= 2.0 * ULN
  17. 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.
  18. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).
  19. Patients must have received prior anti-estrogen therapy in the adjuvant setting.
  20. Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology).
  21. Patients must consent to biopsies.

Exclusion Criteria:

  1. 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
  2. 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).
  3. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy.
  4. 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.
  5. Active or untreated brain metastasis
  6. Pleural or pericardial effusion of any grade
  7. Bone only metastases
  8. Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease).
  9. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed).
  10. 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
  11. 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).
  12. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy.
  13. 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.
  14. Active or untreated brain metastasis
  15. Pleural or pericardial effusion of any grade
  16. Bone only metastases
  17. Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease).
  18. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00903006     History of Changes
Other Study ID Numbers: 2008-0336
Study First Received: May 13, 2009
Results First Received: June 27, 2014
Last Updated: January 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Breast
Hormone receptor-positive metastatic breast cancer
Fulvestrant
Faslodex
MK-0646
Dasatinib
BMS-354825
Sprycel
Adjuvant hormonal therapy

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Dasatinib
Estradiol
Fulvestrant
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Estrogens
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015