Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	Pharmaceutical / Industry	MDX1411-01 NCT00656734

Trial Description

Summary

The purpose of this study are to determine the safety profile of MDX-1411; determine the maximum tolerated dose (MTD); and determine the dose-limiting toxicity (DLT) of MDX-1411 when administered every 14 days to subjects with advanced or recurrent clear cell renal cell carcinoma (ccRCC).

Further Study Information

This is a Phase 1, open-label, multicenter, dose-escalation, multidose study of MDX-1411, a fully human nonfucosylated monoclonal antibody targeting the CD70 transmembrane cell-surface protein which is highly expressed in ccRCC. Up to 40 subjects with measurable ccRCC will be enrolled in the study. Other investigational agents for any reason may not be used while the subject is on study.

Five doses are planned and include: 0.2, 1, 3, 10, and 20 mg/kg/dose. Subjects will be assigned to a dose level in the order of study entry. Initially, 3 subjects will be enrolled at each dose level; up to 6 subjects may be assigned to each dose level, depending upon dose-limitling toxicitiies (DLTs) seen. An additional 10 subjects will be enrolled at the MTD or the the highest dose studied if the MTD is not identified. Dose-limiting toxicities experienced after Cycle 1 in a cohort (delayed DLTs) that are likely or definitely related to therapy with MDX-1411 will be collected and evaluated by the Investigators and Medarex on an ongoing basis. If 4 or more such delayed DLTs are noted, accrual will be held pending safety analysis and will be restarted only with Investigator and Medarex approval. The first cohort of 3 subjects will receive 0.2 mg/kg/dose administered as an intravenous (i.v.) infusion every 14 days for a total of 3 infusions (Days 1,15,and 29). Provided that no subject experiences a DLT, defined ≥ Grade 3 toxicity using NCI Common Toxicity Criteria within the first cycle (42 days) of dosing, the next cohort of 3 subjects will receive the next highest MDX-1411 dose. If 1 of 3 subjects experiences a DLT, the cohort of subjects at that dose level will be expanded to 6 subjects. If at least 2 subjects (of a cohort of up to 6 subjects) experience a DLT during the first cycle (42 days) of dosing, that cohort will have exceeded the MTD. If the previous dose level was well tolerated and no subjects experienced a DLT at that level, 3 additional subjects will be enrolled in that cohort. Depending on the toxicity, an intermediate dose level may be identified by a protocol amendment.

The MTD will be the highest dose where no more than 1 of 6 subjects has experienced a DLT. A DLT will be considered possibly, probably, or definitely related to study drug unless there is a clear, well-documented, altermative explanation for the toxicity.

Eligibility Criteria

Inclusion Criteria:

• Must be 18 years of age or older;

• Life expectancy ≥ 12 weeks;

• Histologically confirmed diagnosis of RCC(clear cell component) with advanced or recurrent disease that is not amendable to cure by surgery or other means and must have failed at least 1 prior systemic therapy, including but not limited to treatment with Sunitinib, Temsirolimus, Sorafenib,IL-2 and/or chemotherapy

• Measurable disease with at least 1 unidimensional measurable lesion per RECIST guidelines with modifications

• May have been treated with up to 3 prior systemic therapies for advanced/recurrent disease or have become intolerant to a systemic therapy

• Subjects with treated brain metastases must be without MRI evidence of progression for at least 8 weeks and off steroids for at least 4 weeks

• May have been treated with radiation therapy (RT) provided there are measurable lesions outside the field of RT

• At least 28 days since the last chemotherapy, immunotherapy, biological or investigational therapy, radiation, or at least 2 weeks from approved TKI therapy (Sunitinib, Sorafenib) prior to the first dosing of MDX-1411 and have recovered from any toxicity associated with such treatment

• At least 28 days prior to the first dose of MDX-1411 since any major surgery

• ECOG Performance Status 0 to 1

• Screening laboratory values must meet specified criteria

• Women must meet 1 of the following criteria:post-menopausal for at least 2 years; surgically incapable of bearing children (have had a hysterectomy or bilateral oophorectomy); or utilizing a reliable form of contraception

• Men must agree to the use of male contraception for at least 70 days after the last dose of study drug

Exclusion Criteria:

• Previous treatment with any other anti-CD70 antibody

• Any other malignancy, excluding basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or localized prostate cancer, from which the subject has not been disease-free for at least 5 years

• Active infection (viral, bacterial, or fungal) requiring i.v. systemic therapy within 28 days of enrollment

• Evidence of bleeding diathesis or coagulopathy

• Active autoimmune disease requiring immunosuppressive therapy

• Known current drug or alcohol abuse

• Apparent active or latent tuberculosis (TB) infection as indicated by any of the following:PPD recently converted to positive;chest x-ray with evidence of infections infiltrate; recent changes in fever/chill patterns

• Any underlying medical condition which, in the principle Investigator's opinion, will make the administration of MDX-1411 hazardous or obscure the interpretation of adverse events

• Psychiatric illness or social situation that would preclude study compliance

• Pregnant or nursing

Trial Contact Information

Trial Lead Organizations/Sponsors

Medarex, Incorporated

Lewis J. Cohen, MD

Study Director

Ralphie Nelson-Morris

Ph: 1-908-479-2611

U.S.A.
Nevada
	Las Vegas
	Nevada Cancer Institute
		Wolfram Earl Samlowski	Principal Investigator
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Glenn S Kroog, MD	Principal Investigator
Ohio
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Brian I. Rini	Principal Investigator
Oregon
	Portland
	Providence Cancer Center at Providence Portland Medical Center
		Brendan D Curti, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00656734
Information obtained from ClinicalTrials.gov on March 18, 2009