Official Title: “An Open-Label Study of KW-2871 Administered With a Premedication Regimen in Patients With Advanced Stage IV Melanoma”

This is a dose escalating cohort study to determine the maximum tolerated dose (MTD) of KW-2871 (in dose cohorts of 60, 80, and 100 mg/m2) when administered with a specified premedication regimen (ranitidine, diphenhydramine, and dexamethasone). KW-2871 will be administered at 14-day intervals.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

This open label study consists of two parts. Part I, the Phase I component of the study, will be conducted at a single center, and will enroll up to 18 patients with histologically documented Stage IV melanoma (per the American Joint Committee on Cancer [AJCC] criteria) that is not currently amenable to surgical resection or other therapies.

A specified premedication regimen consisting of ranitidine, diphenhydramine, and dexamethasone will be administered to all patients 30 minutes prior to infusion of any dose of KW-2871.

Planned doses of KW-2871 are 60 mg/m2, 80 mg/m2, 100 mg/m2

After identification of the MTD, 30 patients will be enrolled at that dose level in Part II of the study. If no MTD is identified after treatment with the 100 mg/m2 dose level, the dose administered in Part II of the study will be 100 mg/m2. If the MTD is determined as 60 mg/m2, this study will be closed to further patient accrual and will not proceed to Part II.

Intervention(s) in this Clinical Trial

• Drug: KW-2871

Primary Measures

• To determine the MTD and a recommended Phase II dose of KW-2871 administered with a specified premedication regimen (rantidine, diphenhydramine, and dexamethasone) in patients with Stage IV melanoma.

Secondary Measures

• To characterize the safety and tolerability profile of KW-2871 when administered with a specified premedication regimen.
• To obtain a preliminary assessment of antineoplastic activity of KW-2871, as measured by the number of objective antitumor responses, duration of response, time to progression (TTP) and survival in this patient population.
• To characterize the pharmacokinetic profile of indicated dose levels of KW-2871 when administered with this specified premedication regimen.

Inclusion Criteria:

• 1. Male or female patients > 18 years of age
• 2. Patients with documented Stage IV melanoma (histologically- or cytologically-proven, as per AJCC criteria) that is not currently amenable to surgical resection (due to either medical contraindication or non-resectability of tumor)
• 3. Patients may have measurable or non-measurable disease, in accordance with the RECIST criteria.
• 4. Failure of at least one, but no more than 3, standard treatment regimen(s) for metastatic disease
• 5. Patients must have adequate end-organ function including:
• 1. Hemoglobin > 9.0 g/dL
• 2. ANC > 1500/mm3
• 3. Platelet count > 100,000/ mm3
• 4. Serum creatinine < 1.5x the upper limit of normal
• 5. Total bilirubin < 1.5 mg/dL
• 6. AST or ALT < 3 X the upper limit of normal
• 7. Serum albumin > 2.5 g/dL
• 6. Patients with an ECOG performance status of 0, 1, or 2, and an expected survival of >
• 12 weeks
• 7. Patients must be able to provide written informed consent (must be obtained at time of patient screening)
• 8. Female patients of childbearing potential must not be pregnant or breast-feeding and must have a negative serum pregnancy test within 72 hours prior to administration of the first dose of KW-287. Women are NOT considered of child-bearing potential after surgical sterilization with physician-documented hysterectomy or tubal ligation, or if post-menopausal; post-menopausal status is defined as absence of menses for at least two consecutive years and a serum FSH > 30 IU/L in the absence of hormone replacement therapy
• 9. At least four weeks from last dose of systemic chemotherapy (6 weeks if mitomycin C or a nitrosourea) and recovery from any acute toxicity
• 10. At least four weeks from last radiotherapy treatment, with recovery from any acute toxicity

Exclusion Criteria:

• 1. Women who are pregnant or lactating and women of childbearing potential and fertile men not agreeing to a medically effective method of contraception. Women of childbearing potential will be informed as to the potential risk of procreation while participating in this study and will be advised that they must use effective contraception (e.g. oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods such as condom and diaphragm, condom and foam, condom and sponge or intra-uterine devices) during the treatment period and for a period of 3 months following the completion of dosing.
• 2. Patients with significant cardiovascular disease as defined by The New York Heart
• Association Classification (Class III or higher)
• 3. Patients with symptomatic or known brain metastases unless patient has undergone radiotherapy (or treatment with gamma knife) or resection of an isolated lesion and maintenance steroids are not required
• 4. Patients with a history of another malignancy within the last 2 years with the exception of:
• Treated, non-melanoma skin cancers
• Carcinoma in situ of the breast or cervix
• History of T1a or b carcinoma of the prostate detected incidentally and comprising <5% of resected tissue, with PSA within normal limits since resection
• 5. Patients with any uncontrolled infection or other intercurrent illness
• 6. Patients with any history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of an underlying disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications
• 7. Patients with known HIV infection
• 8. Patients with inadequate recovery from any prior surgical procedure
• 9. Patients with psychiatric disorders or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies
• 10. Patients with any prior monoclonal antibody therapy for melanoma
• 11. Patients previously treated with any other immunotherapy, vaccine, or biological response modifier therapy for melanoma, either during or within four weeks prior to study entry
• 12. Patients with systemic hormonal therapy, either during or within four weeks prior to first dose of KW-2871, unless for appetite stimulation
• 13. Patients requiring maintenance systemic steroid therapy for any condition
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Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Kyowa Pharmaceutical

Overall Clinical Trial Officials and Contacts

Andres Forero, MD Principal Investigator Comprehensive Cancer Center University of Alabama  

Information obtained from ClinicalTrials.gov on August 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00199342

Study ID Number: 2871-US-002

ClinicalTrials.gov Identifier: NCT00199342

Health Authority: United States: Food and Drug Administration