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

June 27, 2016 updated by: Alliance for Clinical Trials in Oncology

A Pilot Study of Low-Dose Interleukin-2 Plus Recombinant Human Anti-HER2 Monoclonal Antibody in Solid Tumors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

355

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Cycle 1 1st MoAb tx (Day 7), then Day 1 of ea subsequent cycle

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
pre registration, days 1 & 4 ; of cycle 3, repeat prn at cycle 4
Lymphocyte phenotyping
Time Frame: Days 1 & 4 of cycle 3; repeat prn in cycle 4
Days 1 & 4 of cycle 3; repeat prn in cycle 4
Anti tumor response
Time Frame: pre registration; post tx: q 8 wks until progression or death
Tumor measurement
pre registration; post tx: q 8 wks until progression or death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 1997

Primary Completion (Actual)

March 1, 2000

Study Completion (Actual)

April 1, 2002

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 16, 2004

First Posted (Estimate)

July 19, 2004

Study Record Updates

Last Update Posted (Estimate)

June 28, 2016

Last Update Submitted That Met QC Criteria

June 27, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-9661
  • CLB-9661
  • CDR0000065541 (Registry Identifier: NCI Physician Reference Desk)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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