Interleukin-2 Plus Monoclonal Antibody Therapy in Treating Patients With Solid Tumors

NCT ID: NCT00002994

Last Updated: 2016-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

355 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-07-31

Study Completion Date

2002-04-30

Brief Summary

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RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill solid tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Pilot study to examine the effectiveness of interleukin-2 plus monoclonal antibody in treating patients who have solid tumors.

Detailed Description

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OBJECTIVES: I. Determine the toxic effects of humanized anti-HER2 monoclonal antibodies when administered in combination with interleukin-2 (IL-2) in patients with solid tumors. II. Measure in vitro cytotoxicity using peripheral blood mononuclear cells, plasma, and target cell lines that express HER2 in this patient population. III. Phenotypically characterize effector cells at the time of antibody administration and 24 hours after three days of intermediate dose IL-2 pulsing in these patients. IV. Measure antitumor response in these patients.

OUTLINE: Cohorts of 6 patients are enrolled at 4 antibody dose levels. After at least 6 patients have been treated on study for at least 30 days, the next dose level may be initiated provided that fewer than 2 of the first 6 evaluable patients experience dose limiting toxicity (DLT) related to either the antibody or the combination of antibody with interleukin-2 (IL-2). If 2 or more patients experience DLT, the next cohort is enrolled at the antibody dose midway between the current and previous dose levels. An additional 6 patients are entered at the maximum tolerated dose. On course 1, patients receive IL-2 subcutaneously (SQ) daily on days 1-7 and humanized anti-HER-2 monoclonal antibodies IV over 90 minutes on day 7. Patients receive intermediate dose pulsed IL-2 SQ on days 8-10 and low dose IL-2 SQ on days 11-20. On course 2 and all subsequent courses, patients receive humanized anti-HER2 monoclonal antibodies IV immediately prior to IL-2 (SQ) on day 1 and intermediate dose pulsed IL-2 (SQ) on days 1-3. Patients receive low dose IL-2 (SQ) on days 4-14. Treatment may be delayed up to 7 days to allow for recovery and for tumor restaging, but daily low dose IL-2 is continued in this interval. Patients are followed at 4 weeks and then every 8 weeks until progression or death.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

Conditions

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Unspecified Adult Solid Tumor, Protocol Specific

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Monoclonal antibody + interleukin 2

Cycle 1: low dose IL2 days 1-7; MoAb day 7; intermediate dose IL-2 days 8-10; Low dose IL2 days 11-20.

Cycle 2 \& all subsequent cycles: MoAb day 1; intermediate dose IL2 days 1-3; low dose IL2 days 4-14

Group Type EXPERIMENTAL

interleukin 2

Intervention Type BIOLOGICAL

low dose: 1 million IU/square meter subq injection q day days 1-7 and 11-20 cycle 1; days 4-14 subsequent cycles Intermediate dose: 12 million IU/square meter subq injection on days 8-10 of cycle 1; days 1-3 of subsequent cycles

rhuMAb

Intervention Type BIOLOGICAL

90 min IV infusion day 7 of each cycle

Interventions

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interleukin 2

low dose: 1 million IU/square meter subq injection q day days 1-7 and 11-20 cycle 1; days 4-14 subsequent cycles Intermediate dose: 12 million IU/square meter subq injection on days 8-10 of cycle 1; days 1-3 of subsequent cycles

Intervention Type BIOLOGICAL

rhuMAb

90 min IV infusion day 7 of each cycle

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed nonhematologic malignancy Refractory disease or disease for which no effective standard therapy exists HER2 overexpression in tumor tissue Measurable or evaluable disease No CNS metastases Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance status: CALGB 0-1 Life expectancy: At least 3 months Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times normal SGOT no greater than 5 times normal Alkaline phosphatase no greater than 5 times normal Renal: BUN no greater than 1.5 times normal Creatinine no greater than 1.5 times normal Cardiovascular: No uncontrolled or severe cardiac disease LVEF at least 45% by MUGA or echocardiogram Other: HIV negative No immunologic disease (e.g., autoimmune disease) Negative viral hepatitis antibodies No psychiatric conditions which would prevent compliance with treatment Not pregnant or nursing Fertile patients must use effective contraception No active uncontrolled bacterial, viral, or fungal infection Prior or concurrent malignancy allowed

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior interleukin-2 (IL-2) and/or herceptin allowed No concurrent immunosuppressive drugs or other immunomodulators (other than IL-2) Chemotherapy: At least 6 weeks since nitrosoureas, melphalan, or mitomycin More than 4 weeks since other chemotherapy Endocrine therapy: No concurrent corticosteroids Radiotherapy: More than 4 weeks since prior radiotherapy Surgery: At least 4 weeks since major surgery
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gini Fleming, MD

Role: STUDY_CHAIR

University of Chicago

Locations

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University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Countries

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United States

References

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Fleming GF, Meropol NJ, Rosner GL, Hollis DR, Carson WE 3rd, Caligiuri M, Mortimer J, Tkaczuk K, Parihar R, Schilsky RL, Ratain MJ. A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin 2: report of cancer and leukemia group B 9661. Clin Cancer Res. 2002 Dec;8(12):3718-27.

Reference Type RESULT
PMID: 12473581 (View on PubMed)

Fleming GF, Meropol NJ, Hollis DR, et al.: Phase I trial of recombinant human anti-Her2 monoclonal antibody (H) plus low-dose interleukin-2 (IL-2) in patients with solid tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A710, 1999.

Reference Type RESULT

Other Identifiers

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CLB-9661

Identifier Type: -

Identifier Source: secondary_id

CDR0000065541

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-9661

Identifier Type: -

Identifier Source: org_study_id

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