Monoclonal Antibody Therapy in Treating Patients With Metastatic Renal Cell Cancer

A Phase II Open-Label Study of Single Agent MDX-010 for the Treatment of IL-2 Refractory or IL-2 Ineligible Patients With Stage IV Renal Cancer

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have metastatic renal cell cancer (kidney cancer) that is refractory to treatment with interleukin-2 or unable to be treated with interleukin-2.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Biological: ipilimumab

Detailed Description

OBJECTIVES:

• Determine the activity of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody in patients with metastatic clear cell renal cancer who are refractory to or ineligible for interleukin-2.
• Determine the impact of this drug on T-cell number and phenotype in these patients.

OUTLINE: This is an open-label study.

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody IV over 90 minutes once every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with an ongoing partial response may receive additional courses of therapy.

Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually until disease progression.

PROJECTED ACCRUAL: A total of 21-103 patients will be accrued for this study within 2-4 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV clear cell renal carcinoma
• At least 1 site of measurable disease

• Meeting criteria for 1 of the following:

  • Disease progression after prior interleukin-2 (IL-2)
  • Ineligible for standard high-dose IV IL-2 due to comorbid medical conditions
  • Minimal disease (lesions ≤ 3 cm that do not pose risk to organ function) such that participation in this study is not likely to compromise the patient's opportunity to receive future high-dose IL-2
  • Indolent disease (defined as an increase in tumor size of < 50% within the past 6 months) such that participation in this study is not likely to compromise the patient's opportunity to receive future high-dose IL-2
  • No true papillary, medullary, chromophobe, collecting duct, or oncocytic renal cancer

PATIENT CHARACTERISTICS:

Age

• 16 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 3 months

Hematopoietic

• WBC ≥ 2,500/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Hematocrit ≥ 30%

Hepatic

• AST ≤ 3 times upper limit of normal (ULN)
• Bilirubin ≤ ULN (< 3.0 mg/dL for patients with Gilbert's syndrome)
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine < 2.0 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other malignancy except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or any other cancer from which the patient has been disease free for at least 5 years
• No autoimmune disease (including uveitis and autoimmune inflammatory eye disease)
• No active uncontrolled infection
• No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
• At least 3 weeks since prior immunotherapy for renal cancer

Chemotherapy

• At least 3 weeks since prior chemotherapy for renal cancer
• No concurrent chemotherapy

Endocrine therapy

• At least 3 weeks since prior hormonal therapy for renal cancer
• More than 4 weeks since prior corticosteroids
• No concurrent systemic or topical corticosteroids

Radiotherapy

• At least 3 weeks since prior radiotherapy for renal cancer

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 3 weeks since other prior therapy for renal cancer
• No concurrent immunosuppressive agents (e.g., cyclosporine and its analog)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (ACTUAL): October 1, 2007
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: April 7, 2003
• First Submitted That Met QC Criteria: April 8, 2003
• First Posted (ESTIMATE): April 9, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): March 15, 2012
• Last Update Submitted That Met QC Criteria: March 14, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; clear cell renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: 030094; 03-C-0094; CDR0000285624