A Pilot Study of Low-Dose Interleukin-2 Plus Recombinant Human Anti-HER2 Monoclonal Antibody in Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Pilot Study of Low-Dose Interleukin-2 Plus Recombinant Human Anti-HER2 Monoclonal Antibody in Solid Tumors
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity
Outcome Description:
toxicity of anti-Her2 MoAB given in combo w/ IL-2
Outcome Time Frame:
Cycle 1 1st MoAb tx (Day 7), then Day 1 of ea subsequent cycle
Safety Issue:
Yes
Principal Investigator
Gini F. Fleming, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Chicago
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000065541
NCT ID:
NCT00002994
Start Date:
July 1997
Completion Date:
April 2002
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
| University of Massachusetts Memorial Medical Center | Worcester, Massachusetts 01655 |
| Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina 27599-7295 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Comprehensive Cancer Center of Wake Forest University Baptist Medical Center | Winston-Salem, North Carolina 27157-1082 |
| Arthur G. James Cancer Hospital - Ohio State University | Columbus, Ohio 43210 |
| Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| Rhode Island Hospital | Providence, Rhode Island 02903 |
| Vermont Cancer Center | Burlington, Vermont 05401-3498 |
| CCOP - Southern Nevada Cancer Research Foundation | Las Vegas, Nevada 89106 |
| University of California San Diego Cancer Center | La Jolla, California 92093-0658 |
| UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida 33140 |
| Marlene & Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201 |
| Ellis Fischel Cancer Center - Columbia | Columbia, Missouri 65203 |
| Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
| CCOP - North Shore University Hospital | Manhasset, New York 11030 |
| State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| CCOP - Southeast Cancer Control Consortium | Winston-Salem, North Carolina 27104-4241 |
| University of Tennessee, Memphis Cancer Center | Memphis, Tennessee 38103 |
| Mount Sinai Medical Center, NY | New York, New York 10029 |
| New York Presbyterian Hospital - Cornell Campus | New York, New York 10021 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| North Shore University Hospital | Manhasset, New York 11030 |
| CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. | Syracuse, New York 13217 |
| University of Illinois at Chicago Health Sciences Center | Chicago, Illinois 60612 |
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
