A Randomized, Multi-Dose, Open-Label, Phase II Study of BMS-663513 as a Second-Line Monotherapy in Subjects with Previously Treated Unresectable Stage III or Stage IV Melanoma. Revised Protocol 03, incorporating Protocol Amendment 04 (V1.0, Date 26-Aug-2008), Protocol Amendment 05 (V1.0, Date 20-Nov-2008), and Protocol Amendment 06 (V1.0, date 05-Jan-2009). And Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific (Version 1.0, Date 26-Nov-2007).
- Conditions
- MELANOMAMedDRA version: 9.1Level: LLTClassification code 10025670Term: Malignant melanoma stage IIIMedDRA version: 9.1Level: LLTClassification code 10025671Term: Malignant melanoma stage IV
- Registration Number
- EUCTR2007-003993-24-DK
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
1) Signed Written Informed Consent
a) Voluntary signed and dated IRB/IEC approved informed consent form in
accordance with regulatory and institutional guidelines. This must be obtained
before performing protocol-related procedures that are not part of standard subject
care.
2) Target Population
a) Able to comply with visits/procedures required by the protocol.
b) Life expectancy of at least 3 months from enrollment
c) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
(Protocol Appendix 2)
d) Histologically or cytologically confirmed cutaneous, mucosal or acral lentiginous
melanoma that is radiographically assessable or clinically evaluable; however,
measurable disease is not required for participation in this study
e) Surgically incurable Stage III melanoma, and in-transit or satellite lesions or
Stage IV disease, metastatic to one of the following sites: skin, subcutaneous
tissues, or distant lymph nodes; lung or other visceral sites
f) Subjects must have been previously treated with one line of systemic anti-cancer
therapy (non-experimental or experimental) for metastatic disease, and relapsed,
failed to respond (CR, PR or SD) or did not tolerate that regimen. If the treatment
has been administered as an adjuvant and/or neoadjuvant therapy, the subject
must have documented disease progression from the last treatment and also
received one additional line of systemic therapy for metastatic disease
g) Resolution of all prior therapy-related toxicities to = Grade 1 or to baseline level
h) Recovered from the reversible effects of prior antineoplastic therapy with at least
4 weeks elapsed since the last exposure to cytotoxic chemotherapy, or to
radiotherapy and at least 6 weeks elapsed since exposure to nitrosoureas or
mitomycin C. Subjects treated with fully human anti-CTLA-4 monoclonal
antibodies as immunotherapy regimens (eg, ipilimumab and tremelimumab) must
not have received treatment with such antibodies for at least 8 weeks, and those
treated with chimeric or other fully human monoclonal antibodies must not have
received treatment with such antibodies for at least 4 weeks prior to
randomization. Subjects previously treated with cytokines (eg interferons or IL-2)
or noncytotoxic small molecule drugs (eg, tyrosine kinase inhibitors) must not
have received treatment with these drugs at the time of enrollment and at least 2
weeks prior to randomization.
i) Suitable venous access for the conduct of blood sampling for candidate biomarker
study
j) Adequate organ function, as evidence by the following laboratory values:
• Absolute neutrophil count (ANC) = 1500/µL
• Platelet count = 100 x 103/µL
• Hemoglobin = 9 g/dL
• Calculated creatinine clearance = 40 mL/min based on Cockcroft-Gault or
other available formula.
• AST and ALT = 2.5 x ULN
• Total bilirubin = 1.5 x ULN
3) Age and Sex
a) Men and women, who are at least 18 years of age.
b) Male subjects must be willing to use an appropriate method of barrier
contraception (eg, condoms) and inform any sexual partners that they must also
use a reliable method of contraception (eg, birth control pills) during the study
and for 60 days after the last dose of study treatment.
c) Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 60 days after
the last dose of investigational product in such a manner that the risk of pregnancy
is minimized.
WOCBP include any female who h
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study and for up to 60 days after the last dose of
investigational product.
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to investigational
product administration
d) Sexually active fertile men not using effective birth control if their partners are
WOCBP (eg, males unwilling to use a barrier method of contraception)
2) Target Disease Exceptions
a) Ocular melanoma
b) Complete surgical resection of all identifiable sites of disease
c) Symptomatic brain metastasis. Subjects 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).
Subjects with stable brain metastasis and those who were previously treated with
radiotherapy or surgery must have no current evidence of symptomatic brain
metastasis and are off steroid therapy for at least 4 weeks prior to randomization.
d) Any other malignancy for which the subject has been disease-free for less than 5
years, with the exception of adequately treated basal or squamous cell skin cancer,
superficial bladder cancer or carcinoma in situ of the cervix, breast or prostate
3) Medical History and Concurrent Diseases
a) Histories of autoimmune diseases including Inflammatory Bowel Disease,
Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease are excluded
from this study. Note that not all autoimmune diseases are to be excluded, and
subjects with a history of well-controlled and/or clinically manageable
autoimmune disease (eg, vitiligo, well-controlled thyroid disease, or mild
psoriasis) may be considered for inclusion in consultation with the Medical
Monitor
b) Known or suspected human immunodeficiency virus (HIV) infection or known or
suspected active or chronic hepatitis B or hepatitis C infection. If false positive
results are obtained, the subject can enter the study after discussion and agreement
between the Investigator and the Medical Monitor.
c) Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of the investigational drug.
d) Clinically significant abnormalities or serious cardiac arrhythmias on 12-lead
electrocardiogram (ECG). Significant cardiovascular impairment (eg, history of
congestive heart failure), New York Heart Association (NYHA) (Appendix 3)
Class III and IV or history of myocardial infarction or unstable angina within the
past six months or significant vascular disease (eg, aortic aneurysm or aortic
dissection)
e) History of abdominal fistula or gastrointestinal perforation within 6 months prior
to randomization
f) Prior treatment with radiation therapy within 4 weeks involving > 25% of the
hematopoietically active bone marrow
4) 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) Bodyweight of less then 85 lbs (38.5 Kg)
5) Allergies and Adverse Drug Reactions
a) History of allergy to BMS-663513 or related compounds
6) Prohibited Treatments and/or Therapies
a) Received more than one line of prior systemic therapies including cytotoxic
chemotherapy; non-cytoxic sma
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