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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002994
Recruitment Status : Completed
First Posted : July 19, 2004
Last Update Posted : June 28, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Biological: interleukin 2 Biological: rhuMAb Phase 1

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 355 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Low-Dose Interleukin-2 Plus Recombinant Human Anti-HER2 Monoclonal Antibody in Solid Tumors
Study Start Date : July 1997
Actual Primary Completion Date : March 2000
Actual Study Completion Date : April 2002

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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

Biological: 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

Biological: rhuMAb
90 min IV infusion day 7 of each cycle

Primary Outcome Measures :
  1. Toxicity [ Time Frame: Cycle 1 1st MoAb tx (Day 7), then Day 1 of ea subsequent cycle ]
    toxicity of anti-Her2 MoAB given in combo w/ IL-2

Secondary Outcome Measures :
  1. In vitro cytotoxicity [ Time Frame: pre registration, days 1 & 4 ; of cycle 3, repeat prn at cycle 4 ]
    patient PBMC and plasma with target HER2 expressing cell lines

  2. Lymphocyte phenotyping [ Time Frame: Days 1 & 4 of cycle 3; repeat prn in cycle 4 ]
  3. Anti tumor response [ Time Frame: pre registration; post tx: q 8 wks until progression or death ]
    Tumor measurement

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002994

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Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Gini Fleming, MD University of Chicago

Publications of Results:
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.

Responsible Party: Alliance for Clinical Trials in Oncology Identifier: NCT00002994     History of Changes
Other Study ID Numbers: CALGB-9661
CDR0000065541 ( Registry Identifier: NCI Physician Reference Desk )
First Posted: July 19, 2004    Key Record Dates
Last Update Posted: June 28, 2016
Last Verified: June 2016

Keywords provided by Alliance for Clinical Trials in Oncology:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents