A Phase 1/2, Ascending Multiple-Dose Study to Evaluate the Safety, Efficacy andPharmacokinetics of BMS-753493 in Subjects with Advanced Cancer.Revised Protocol 04, incorporating Protocol Amendment 02 (v1.0, Date 16-Oct-2007), 03 (v1.0, Date 26-Nov-2007), 04 (v2.0, Date 20-May-2008), and 05 (v3.0, date 24-Mar-2009). And Pharmacogenetics Blood Sample Amendment 01 - Site specific (version 2.0, Date 16-Jul-2007).
- Conditions
- Advanced cancerMedDRA version: 9.1Level: LLTClassification code 10048683Term: Advanced cancer
- Registration Number
- EUCTR2007-001433-34-GB
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 105
Phase 1:
1) Signed Written Informed Consent
a) The signed informed consent form.
2) Target population
a) Histologically or cytologically confirmed diagnosis of solid tumor malignancy which
has progressed on standard therapy or for whom no standard therapy is known;
i) Minimum availability of 10 archived tumor tissue slides, or subject’s
willingness and ability to undergo tumor biopsy collection for IHC analysis; either available within 28 days or greater from Cycle 1 Day 1;
b) Measurable or non-measurable disease as defined by RECIST criteria;
c) Adequate recovery from recent surgery and radiation therapy. At least one week
must have elapsed from the time of a minor surgery and at least 3 weeks for major
surgery and radiation therapy;
d) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Protocol Appendix 3);
e) Available for treatment and follow-up. Subjects enrolled in this trial must be
treated at the participating center;
f) At least four weeks must have elapsed from the last dose of carboplatin,
immunotherapy or chemotherapy, (six weeks for nitrosoureas, or mitomycin C),
prior to beginning protocol therapy. Hormonal anti-cancer agents and
nontraditional cytotoxic agents, such as trastuzumab, gefitinib, erlotinib,
cetuximab, bevacizumab, are not considered chemotherapy regimens when
administered alone, and at least 4 weeks must have elapsed from the last dose of
this class of agents before study drug administration. Subjects must have
recovered to baseline or Grade 1 from the toxicities resulting from previous
therapies.
3) Age and Sex
a) Men and women, ages 18 and greater;
Phase 2 includes the above inclusion criteria and the following:
Subjects with measurable, confirmed, advanced ovarian (including primary peritoneal or fallopian tube), renal cell or breast cancer or non-measurable, confirmed, advanced ovarian (including primary peritoneal or fallopian tube) cancer with CA125 = 2x ULN, which has progressed on standard therapy or for whom no standard therapy is known, in place of:
- Histologically or cytologically confirmed diagnosis of solid tumor malignancy which has progressed on standard therapy or for whom no standard therapy is known.
• IHC will be utilized to select subjects prospectively for assignment to the FR+
and FR- groups.
• For subjects with renal cell cancer, up to 3 prior treatment regimens are permitted,
and for subjects with ovarian cancer up to 4 prior treatment regimens are permitted. For subjects with breast cancer, up to 4 prior cytotoxic treatment regimens, with no more than 3 in the advanced disease setting, are permitted. Hormonal therapies are not included in these counts of previous treatment regimens.
- If a treatment is stopped and restarted after a disease recurrence, that will be
counted as 2 regimens.
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
Phase 1
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period as per the Investigator’s discretion to avoid
pregnancy throughout the study and for up to 4 weeks after the study in such a
manner that the risk of pregnancy is minimized.
b) WOCBP using a contraceptive method deemed inappropriate by the Investigator.
c) Women who are pregnant or breastfeeding
Phase 1
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period as per the Investigator’s discretion to avoid
pregnancy throughout the study and for up to 4 weeks after the study in such a
manner that the risk of pregnancy is minimized.
b) WOCBP using a contraceptive method deemed inappropriate by the Investigator.
c) Women who are pregnant or breastfeeding
on thyroid replacement therapy and whose symptoms of thyroiditis are resolved to
= Grade 1 before enrollment are eligible;
i) Any other sound medical, psychiatric and/or social reason as determined by the
Investigator.
3) Physical and Laboratory Test Findings
a) Inadequate hematologic function with absolute neutrophils <1,500/mm3, platelets
<100,000/mm3, or hemoglobin <10 g/dL;
b) Inadequate hepatic function with serum bilirubin =1.5 times the upper
institutional limits of normal, ALT = 2.5 times the upper institutional limits of
normal, AST = 2.5 times the upper institutional limits of normal;
c) Inadequate renal function defined as a calculated creatinine clearance of < 60
mL/min according to the Cockcroft-Gault formula:
i) In men: [eGFRCG(mL/min)]=(140 - age) x weight (kg) / (72 x serum
creatinine concentration in mg/dL)
ii) In women, multiply this result by 0.85
d) Inadequate thyroid function with free T4 and/or TSH outside of the institutional
limits of normal unless approved by Medical Monitor.
4) Allergies and Adverse Drug Reactions
a) History of any significant drug allergy which in the Investigator’s discretion
would inhibit the subject’s participation.
5) Prohibited Treatments and/or Therapies
a) Exposure to any investigational drug or placebo within 4 weeks of study drug
administration;
b) Use of multi-vitamins and/or folic acid supplements for 1 week prior to Cycle 1
Day 1 and throughout the course of the trial;
c) Other concurrent chemotherapy hormonal therapy, immunotherapy regimens or
radiation therapy, standard or investigational;
d) Prior radiation must not have included =25% of major bone marrow containing
areas (pelvis, lumbar spine);
e) Use of steroids except in the following instances, in which the use of steroids is allowed:
• for anti-emetic purposes.
• continuing therapy for controlled brain metastases.
• chronic steroid use in the context of a disease requiring such use .
• for appetite stimulation.
• Treatment of a hypersensitivity reaction and as subsequent premedication for the
prevention of same
• Premedication prior to CT scan requiring IV contrast dye in subjects with IV contrast
dye allergy
• Other uses of steroids may be allowed with prior approval from the Medical Monitor
f) The use of known P-gp-inhibitors (Prot. App. 8) is prohibited for 1 week prior to
Cycle 1 Day 1 and throughout the course of the trial.
6) Other
a) Inability to provide an archived tumor sample (10 slides) for analysis within 28
days of study drug administration;
b) Prisoners or involuntarily incarcerated subjects;
c) Subjects who are compulsorily detaine
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