A Phase I/II, Ascending, Multi-Dose Study of BMS-663513, An Agonistic Anti-CD137Monoclonal Antibody, Administered Every Three Weeks to Patients with Metastatic orLocally Advanced Solid Malignancies.Revised Protocol Number 07, incorporating Amendments 01, 02, 03, 04, 05, 06, 07 and Administrative Letter Dated 10-Mar-2006.
- Conditions
- Patients with Metastatic or Locally Advanced Solid MalignanciesMedDRA version: 9.1Level: LLTClassification code 10025650Term: Malignant melanomaMedDRA version: 9.1Level: LLTClassification code 10038395Term: Renal carcinomaMedDRA version: 9.1Level: LLTClassification code 10033131Term: Ovarian carcinoma
- Registration Number
- EUCTR2007-000416-91-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 110
- Signed written informed consent
- Target population
a) Able to comply with visits/procedures required by the protocol
b) Life expectancy of at least 3 months
c) ECOG performance status score 0 - 1 (Protocol Appendix 4).
d) Patients with histologic or cytologic diagnosis of an advanced solid malignancy
who have failed, refused or are unable to receive standard treatment.
NOTE: Patients enrolled after Amendment 7 is IRB approved are limited to:
• Melanoma (must be anti-CTLA-4 naive),
• Renal (clear cell) carcinoma, or
• Epithelial carcinoma arising from the ovary, fallopian tube or peritoneum.
e) At least 1 site of measurable disease (excluding epithelial carcinoma who must
have at least 1 site of evaluable” disease)
f) A tumor paraffin embedded tissue block or 5 - 15 unstained slides from the tumor
tissue block (from the primary or a metastatic tumor) must be provided for
biomarker and predictive marker analyses. Note: If the tumor tissue block or unstained slides are not available or insufficient, additional fresh tumor tissue
could be collected during the optional pretreatment biopsy to satisfy this criteria
g) At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy,
hormonal therapy, radiotherapy or major surgery, & the 1st day of BMS-663513 therapy. At least 6 weeks for nitrosoureas, mitomycin C & liposomal doxorubicin
h) Toxicities related to prior therapy must either have returned to = Grade 1, baseline or deemed irreversible
-Age and Sex
a) Men and women, who are at least 18 years of age.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche & who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 IU/mL. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an
intrauterine device or barrier methods (diaphragm, condoms, spermicides) to
prevent pregnancy or practicing abstinence or where partner is sterile (eg,
vasectomy), should be considered to be of child bearing potential.
- WOCBP must have a negative pregnancy test [minimum sensitivity 25 IU/L
or equivalent units of beta-human chorionic gonadatrophin (ßHCG)] within
72-hours prior to the start of study medication.
- Physical and laboratory test findings:
a) Adequate bone marrow function defined as:
Absolute neutrophil count (ANC) >= 1,500 cells/mm³
Platelet count >= 100,000 cells/mm³
Hemoglobin >= 9.0 g/dl
b) Adequate hepatic function defined as:
Total bilirubin =< 1.5 times the institutional upper limit of normal (IULN)
ALT, AST and alkaline phosphatase =< 2.5 times the IULN
c) Adequate renal function defined as:
Serum creatinine =< 1.5 times the IULN or
Calculated creatinine clearance of >= 60 mL/min/1.73m²
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
- Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 12 weeks after the study.
b) WOCBP using a prohibited contraceptive method.
c) Women who are pregnant or breastfeeding.
d) Women with a positive pregnancy test on enrollment or prior to study drug
administration.
e) Sexually active fertile men, whose partners are WOCBP, who are unwilling or
unable to use an acceptable method of birth control from the time of enrollment
and for 12 weeks after participation in the study.
- Medical History and Concurrent Diseases
a) Active infection or uncontrolled significant acute or chronic medical illness other
than current cancer that would prohibit safe administration of BMS-663513.
b) Any concurrent malignancy other than adequately treated basal or squamous cell
skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix.
Patients with a previous malignancy but without evidence of disease for >= 5 years
will be allowed to enter the trial.
c) History of autoimmune diseases including rheumatoid arthritis, lupus
erythermatosus, uveitis and autoimmune inflammatory eye disease, psoriasis,
multiple sclerosis, inflammatory bowel diseases, etc. Type I diabetes mellitus is
allowed.
d) Known or suspected human immunodeficiency virus (HIV) positive.
e) Any current condition requiring the continued use of systemic or topical steroids
or the use of immunosuppressive agents (eg, cyclosporine and its analog, or
chemotherapy agents). All corticosteroid use must have been discontinued
>= 4 weeks prior to Day 1 of treatment.
f) Active/symptomatic brain metastasis. Patients with signs or symptoms suggestive
of brain metastasis are not eligible unless brain metastases are ruled out by
computerized axial tomography (CT) scan or magnetic resonance imaging (MRI).
Patients with stable brain metastasis and those who were previously treated with
radiotherapy or surgery must have no current evidence of active/symptomatic
brain metastasis and are off steroid therapy for at least 4 weeks prior to Day 1 of
treatment.
g) Uncontrolled or significant cardiovascular disease including myocardial infarction
within 6 months, uncontrolled angina, Class III-IV New York Heart Association
(NYHA) congestive heart failure (Appendix 5) and clinically significant
ventricular arrhythmias.
h) Any other sound medical, psychiatric and/or social reason, which in the opinion
of the principal investigator, would prohibit the understanding of the informed
consent and/or make the administration of study drug hazardous or obscure the
interpretation of adverse events.
i) History of hepatitis B or C, or alcohol induced liver disease.
- Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal
in physical examination, vital signs, ECG or clinical laboratory determinations.
b) Positive blood screen for hepatitis B surface antigen, or hepatitis C antibody.
- Allergies and Adverse Drug Reactions
a) History of allergy to BMS-663513 or related compounds.
- Prohibited Therapies and/or Medications
a) Exposure to any investigational products within 4 weeks prior to Day 1 of
treatment.
b) Use of any immunosuppressing treatments including corticosteroids,
cyclosporine, mycophenolate mofetil (CellCept®), chemotherapy, radiation, etc,
within 4 weeks prior to Day 1 of treatment.
-Other Exclusion Criteria
a) Prisoners or patients w
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