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

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00002994
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 355
• Locations: 34
• Arm: 1
• Duration (Months): 57
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: N/A
• 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: Jul 1, 1997
• Actual Primary Completion Date: Mar 1, 2000
• Actual Study Completion Date: Apr 1, 2002

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Toxicity [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 [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 [Days 1 & 4 of cycle 3; repeat prn in cycle 4]

3. Anti tumor response [pre registration; post tx: q 8 wks until progression or death]

   Tumor measurement

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
2	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
3	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
4	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
5	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
6	University of Illinois at Chicago Health Sciences Center	Chicago	Illinois	United States	60612
7	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
8	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
9	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
10	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
11	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
12	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
13	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
14	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
15	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
16	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756
17	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
18	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
19	North Shore University Hospital	Manhasset	New York	United States	11030
20	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
21	New York Presbyterian Hospital - Cornell Campus	New York	New York	United States	10021
22	Mount Sinai Medical Center, NY	New York	New York	United States	10029
23	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13210
24	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
25	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
26	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
27	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
28	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
29	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
30	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
31	Rhode Island Hospital	Providence	Rhode Island	United States	02903
32	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
33	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee	United States	38163
34	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Gini Fleming, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00002994
• Other Study ID Numbers: CALGB-9661; CLB-9661; CDR0000065541
• First Posted: Jul 19, 2004
• Last Update Posted: Jun 28, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Neoplasms; Interleukin-2

Study Results

No Results Posted as of Jun 28, 2016