A Phase 1/2a, Ascending Multiple-Dose Study to Evaluate the Safety, Efficacy andPharmacokinetics of BMS-753493 in Subjects with Advanced Cancer. Revised Protocol 02, incorporating Protocol Amendment 02 (Version 1.0, Date 17-Oct-2007) and 03 (Version 1.0, Date 26-Nov-2007). And Pharmacogenetics Blood Sample Amendment 01 (Version 3.0, Date 14-Aug-2007).
- Conditions
- Advanced CancerMedDRA version: 9.1Level: LLTClassification code 10048683Term: Advanced cancer
- Registration Number
- EUCTR2007-001432-31-NL
- 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
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, (6 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, etc., 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;
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception 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.
Phase 2 includes the above inclusion criteria and the following:
• Subjects with measurable, confirmed, advanced ovarian (including primary
peritoneal), renal cell or breast cancer or non-measurable, confirmed, advanced
ovarian (including primary peritoneal) 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 or breast cancer, up to 4 prior treatment regimens are
permitted.
- 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 unwilling or unable to use an acceptable method to avoid
pregnancy for entire study period as per Investigator’s discretion to avoid
pregnancy throughout study & for up to 4 weeks after study in such a
manner that risk of pregnancy is minimized
b)WOCBP using a contraceptive method deemed inappropriate by Investigator
c)pregnant or breastfeeding Women
d)Women with positive pregnancy test on enrollment or prior to investigational
product administration
e)Sexually active fertile men not using effective birth control if their partners are
WOCBP
2) Medical History and Concurrent Diseases
a)Inability to be venipunctured &/or tolerate venous access
b)Subjects with known symptomatic brain metastasis. Subjects with controlled brain
metastasis will be allowed & steroid therapy may be continued. Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastasis are ruled out by CT or MRI
c)CTCAE Grade 2 or greater neuropathy currently or prior history of Grade 3 or greater neuropathy
d)Psychiatric disorders or other conditions rendering subject incapable of
complying with requirements of protocol
e)Serious intercurrent infections, or nonmalignant medical illnesses that are
uncontrolled or whose control may be jeopardized by complications of this
therapy
f)Uncontrolled or significant cardiovascular disease, including:
i)myocardial infarction within 6 months
ii)uncontrolled angina within 3 months
iii)congestive heart failure within 3 months
iv)diagnosed or suspected congenital LQT syndrome
v)any history of significant arrhythmias (such as ventricular tachycardia,
ventricular fibrillation, or torsades de pointes)
vi) prolonged QTcF on screening or Cycle 1 Day 1 pre-dose mean (QTcF
=450msec)
vii)subjects with pacemaker
viii)2nd degree AV block or any form of BBB
ix)troponin (T or I)> institutional upper limits of normal
x)LVEF< institutional limits of normal as determined by MUGA or
echocardiogram
xi)inadequate cardiac function as defined by a NYHA classification of >Class I;
g)Known MTHFR mutations or known impaired regulation of homocysteine levels;
h)Uncontrolled thyroid disorder, including hypothyroidism, hyperthyroidism,
Grave’s disease or Hashimoto’s disease. Subjects with hypothyroidism who are
on thyroid replacement therapy & whose symptoms of thyroiditis are resolved to
=Grade 1 before enrollment are eligible
i)Any other sound medical, psychiatric &/or social reason as determined by Investigator
3) Physical and Laboratory Test Findings
a)Inadequate hematologic function with absolute neutrophils <1,500/mm³, platelets
<100,000/mm³ or hemoglobin <10g/dL
b)Inadequate hepatic function with serum bilirubin=1.5 x upper institutional limits of normal, ALT = 2.5 x upper institutional limits of normal, AST =2.5 x upper institutional limits of normal
c)Inadequate renal function defined as calculated creatinine clearance of <60mL/min according to 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 &/or TSH outside of institutional limits of normal
4) History of any significant drug allergy which in Investigator’s discretion would inhibit subject’s participation
5) Prohibited Treatments &/or Therapies
a)Exposure to any investigational drug or placebo within 4 weeks of study drug
administration
b)Use of multi-vita
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