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 03 (version 4.0, dated 19-May-10), incorporating Administrative Letters 01, 02 and 03; and Amendment 03, 04 and 05 + Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific (version 1.0 dated 13-Aug-08)
- Conditions
- Advanced or Metastatic Her-2-positive Breast CancerMedDRA version: 12.0 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancerMedDRA version: 12.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
- Registration Number
- EUCTR2009-013766-78-GB
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- 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 in the advanced or metastatic setting. Prior treatment with other Her-2-targeted agents (e.g. lapatinib, pertuzumab, trastuzumab DM-1, neratinib 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)) based on local laboratory results.
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 except for alopecia. 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 anytime during study participation, radiation therapy is allowed to a limited field (eg painful bone metastasis, painful lumps) after consultation with the medical monitor, 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 3 months 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 acceptable method to avoid pregnancy for the entire study period & 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, 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 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, eg 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)Major surgery within 4 weeks of study drug administration
f)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 treatment discontinuation because of significant cardiotoxicity in adjuvant or metastatic setting (interruptions with restart upon recovery allowed)
•Diagnosed or suspected congenital long QT syndrome
•Any history of clinically significant ventricular arrhythmias; controlled AF is not an excl. criterion
j)Subj. with concomitant second malignancies (exc. non-melanoma skin cancers & adequately treated in-situ carcinoma of the cervix), unless complete remission achieved at least 5 years prior to study entry & no additional therapy required/anticipated to be required during study
k)Any other sound medical psychiatric and/or social reason as determined by Investigator
4) Physical & Lab 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
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