A Phase I/II Trial of BMS-754807 in Combination with Trastuzumab (Herceptin®) in Subjects with Advanced or Metastatic Her-2-positive Breast Cancer Revised Protocol Number 01 (version 2.0, dated 01-Jun-09), incorporating Administrative Letter 01 and Amendment 03.+ Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific (version 1.0 dated 13-Aug-08)+ Administrative Letter 02, dated 01-Sep-09
- Conditions
- Advanced or Metastatic Her-2-positive Breast CancerMedDRA version: 12.0Level: LLTClassification code 10065430Term: HER-2 positive breast cancerMedDRA version: 12.0Level: LLTClassification code 10027475Term: Metastatic breast cancer
- Registration Number
- EUCTR2009-013766-78-HU
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 48
1) Signed Written Informed Consent
2) Target Population
a) Subjects with locally advanced or metastatic Her-2-positive breast tumors who have failed at least one trastuzumab containing regimen. Prior treatment with other Her-2-targeted agents (e.g. lapatinib, pertuzumab, trastuzumab DM-1 etc) is allowed. When treatment with Her-2-targeted therapy has stopped, progression should occur within 6 months after last er-2-targeted treatment to be eligible for the dose expansion phase.
b) Histologic or cytologic diagnosis of Her-2-positive breast cancer. Her-2-positivity is defined as either 3+ on immunohistochemistry (uniform, intense membrane staining of > 30% of invasive tumor cells) or FISH-positive (>2.2 ratio: (HER2 gene signals to chromosome 17 signals)).
c) Ability to comply with visits/procedures required by the protocol.
d) Life expectancy of at least 3 months.
e) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix 2)
f) A tumor paraffin tissue block or 20 - 30 unstained slides from the tumor tissue block, cut within one week of shipment, must be provided for biomarker and predictive marker analyses. (This tissue does not need to be obtained fresh at the time of screening. Obtaining archived tumor material or unstained slides from an archived tumor block will suffice to meet this requirement. Archived tumor tissue must be provided during the screening, if a new biopsy is needed this should also occur during screening).
g) Subjects in the dose expansion phase must have measurable disease as defined by RECIST criteria (Appendix 3).
3) Previous Treatment
a) Prior anti-cancer treatments are permitted (ie. chemotherapy, radiotherapy, hormonal, or immunotherapy).
b) Toxicity related to prior anti-cancer therapy and/or surgery must either have resolved, returned to baseline or been deemed irreversible. Four (4) weeks must have elapsed between surgery and/or last dose of prior anti-cancer therapy and the initiation of study therapy.
c) Prior to enrollment (within 4 weeks) or during study participation, radiation therapy is allowed to a limited field (eg painful bone metastasis, painful lumps), if it is not the sole site of measurable and/or assessable disease.
4) Age and Sex
Women, ages 18 years and above.
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study [and for up to 4 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1) Sex & Reproductive Status
a)WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 3 months after the last dose of investigational product (IP).
b)WOCBP using a prohibited contraceptive method.
c)Pregnant or breastfeeding women.
d)Women with positive pregnancy test on enrollment or prior IP administration.
2) Target Disease Exceptions
a)Subj. with known symptomatic brain metastasis. Subj. with controlled brain metastasis will be allowed. Subj. with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI.
b)Any condition requiring chronic use of steroids. Inhalation steroids for mild pulmonary disease eg not leading to exclusion based on other criteria are allowed.
3) Medical History & Concurrent Diseases
a)Serious uncontrolled medical disorder or active infection, which would impair the ability of the subj. to receive protocol therapy.
b)Any disorder with dysregulation of glucose homeostasis incl. but not limited to history of Type 1 or 2 Diabetes Mellitus or prediabetic symptoms, incl. polyuria or polydipsia and delayed healing of wounds, excl. prior hyperglycemia in pregnancy.
c)History of glucose intolerance or conditions with an ancillary effect on glucose, such as Cushing syndrome, pheochromocytoma, acromegaly, aldosteronism, or hyperthyroidism (excl. hyperthyroidism treated and adequately controlled for = 4 weeks before entering the study).
d)Current or recent (within 3 months) gastrointestinal disease that could impact study drug absorption.
e)Any major surgery within 4 weeks of study drug administration.
f)Any gastrointestinal surgery that could impact study drug absorption.
g)Inability to swallow oral medication.
h)Inability to be venipunctured and/or tolerate venous access.
i)Uncontrolled or significant cardiovascular disease incl.:
•Myocardial infarction within 6 months
•Uncontrolled angina within 3 months
•Congestive heart failure within 3 months
•LVEF = the institutional lower limit of normal
•Previous discontinuation of treatment because of cardiotoxicity in either adjuvant or metastatic setting
•Diagnosed or suspected congenital long QT syndrome
•Any history of clinically significant ventricular arrhythmias; controlled atrial fibrillation is not an excl. criterion.
j)Subj. with concomitant second malignancies (except non-melanoma skin cancers and adequately treated in-situ carcinoma of the cervix), unless complete remission was achieved at least 5 years prior to study entry and no additional therapy is required/anticipated to be required during study period
k)Any other sound medical psychiatric and/or social reason as determined by Investigator.
4) Physical & Laboratory Test Findings
a)Fasting blood glucose levels indicating diabetes defined as fasting glucose = 7.0 mmol/L (126 mg/dL).
b)Inadequate bone marrow function defined as:
• Absolute neutrophil count < 1,500 cells/mm³.
• Platelet count < 100,000 cells/mm³.
• Hemoglobin < 9.0 g/dL (5.6 mmol/L).
c)Inadequate hepatic function defined as:
• Total bilirubin > 1.5 times the institutional upper limit of normal (IULN).
• Alanine transaminase (ALT) and aspartate transaminase (AST) > 2.5 times the IULN.
d)Inadequate renal function defined as:
• Serum creatinine > 1.5 times the IULN.
e)Abnormalities in serum sodium, potassium, calcium and magnesium levels = Grade II
5) Allergies & Adverse Drug Reactions
a)History of allergy to compounds chemically
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method