NIH Clinical Research Studies
http://clinicalstudies.info.nih.gov/detail/A_2000-C-0121.html
Protocol Number: 00-C-0121
Active Accrual, Protocols Recruiting New Patients
Title:
A Phase I Investigation of IL-12/Pulse IL-2 in Adults with Advanced
Solid Tumors
Number:
00-C-0121
Summary:
The purposes of this study are fourfold. It will 1) determine what dose
of interleukin-12 (IL-12) and interleukin-2 (IL-2) combination therapy
can be given safely to patients with advanced cancer; 2) evaluate the
side effects of this treatment; 3) examine how the body handles this
drug combination; and 4) determine whether and how the therapy may
cause the immune system to stop or slow tumor growth.
IL-2 is an approved drug for treating melanoma and kidney cancer. IL-12
is an experimental drug that has shown anti-cancer activity in animals,
shrinking tumors and slowing their growth. Animal studies suggest that
given together, the drugs may be more effective against cancer than
either one singly.
Patients 18 years of age and older with advanced solid-tumor cancers
(kidney, breast, lung, sarcomas and others) that do not improve with
standard treatment may qualify for this study. Candidates will have a
physical examination, including blood and urine tests,
electrocardiogram (EKG) and echocardiogram, DTH skin test (to test the
function of the immune system), chest X-ray and lung function tests to
determine eligibility. Bone marrow biopsy and imaging procedures such
as CT and MRI scans may also be required. Patients over 50 years old
will also undergo exercise stress testing.
Treatment will consist of four courses of IL-2 and IL-12. On days one
and nine of each course, patients will receive three doses (one every 8
hours) of IL-2 intravenously (through a vein). On days two, four, six,
10, 12 and 14, they will receive IL-12 intravenously. This will be
followed by a recovery period from days 15 through 35. This regimen
will be repeated for another three cycles; patients who show benefit
without severe side effects may continue for additional cycles.
Treatment for the first cycle will be administered in the hospital. If
the drugs are well tolerated, additional therapy may be given on an
outpatient basis.
A biopsy (removal of a small sample of tumor tissue) will be done at
the beginning of the study, after completing the first treatment cycle,
and possibly again when the cancer slows, stops or gets worse, or if
the patient leaves the study. These tumor samples will be examined to
evaluate the effects of treatment. Several blood samples also will be
collected during the course of treatment to monitor immune system
effects. A device called a heparin lock may be put in place to avoid
multiple needle sticks.
Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): Children
Eligibility Criteria:
INCLUSION CRITERIA:
Adult patients 18 years of age and older.
Pathologically or cytologically-proven diagnosis of non-hematologic
malignancy, and the presence of radiographically or clinically
evaluable disease.
Patients with solid tumors including renal, breast, lung
carcinomas, as well as sarcomas for whom a proven more effective
therapy does not exist. Patients with renal cell carcinoma should
either have specifically declined or be unable or ineligible to recieve
treatment high-dose IL-2.
Patients must not have received myelosuppressive chemotherapy,
hormonal therapy, radiotherapy or immunotherapy within four weeks of
entry onto this protocol.
Estimated life expectancy of at least 12 weeks.
ECOG performance status of 0 or 1.
Patients must be free of acute infection or other significant
systemic illness.
Negative serologic testing for hepatitis B will be required to
limit confounding variables in the assessment of the potential hepatic
toxicity of this combination.
Negative serologic testing for human immunodeficiency virus (HIV)
will be required given the uncertain impact of rhIL-12 and/or rhIL-2
administration on viral replication, and the potential alterations in
immune responsiveness among patients concurrently infected with HIV.
Adequate hepatic and renal function as evidence by:
Transaminases less than 2.5 times the upper limit or normal;
Total serum bilirubin less than 2.0 mg/dl;
Serum Cr less than 2.0 mg/dl or calculated creatinine clearance of
greater than 60 ml/min/1.73M(2).
Adequate bone marrow function (without growth factor support) as
evidence by:
Absolute Neutrophil count (ANC) greater than 1500 cells/mm(3);
Platelets greater than 100,000/mm(3).
For women of childbearing potential, a negative urine pregnancy
test within 14 days prior to initiation of study therapy is required.
For patients of child-bearing potential, contraceptive precautions must
be maintained during study participation.
Normal pulmonary function (as documented by PFTs), and for patients
over the age of 50, normal stress thallium testing. Normal pulmonary
function testing will be defined as DLCO greater than 60% of predicted
and FEVI greater than 70% of predicted.
EXCLUSION CRITERIA:
Critically-ill or medically unstable patients.
History or a presence of brain metastases.
History of coronary artery disease, angina or myocardial infarction.
Presence of clinically significant pleural effusion.
History of malignant hyperthermia are.
Concurrent or history of autoimmune disease.
History of congenital or acquired coagulation disorder.
Patients with a history of ongoing or intermittent bowel
obstruction.
Women who are pregnant or lactating will be excluded.
Systemic corticosteroids, radiotherapy, chemotherapy, or other
investigational agents within 4 weeks prior to study entry.
Patients who have received any of the following agents with known
immunomodulatory effects within 4 weeks prior to study entry:
G-CSF/GM-CSF, interferons or interleukins, growth hormone, IVIG,
retinoic acid.
Patients with a history of previous therapy with rhIL-12 will be
excluded from study participation. For patients with renal cell
carcinoma, a history of therapy with rhIL-2 will not exclude patients
from study participation.
Patients with concurrent administration of any other
investigational agent.
Patients with hematologic malignancies including leukemia or
lymphoma.
History of bone marrow or stem-cell transplantation.
Intercurrent radiation therapy patients will be allowed on study if
in the opinion of the principal investigator(s) its use is not
necessitated by disease progression. For patients with disease
progression, radiation therapy will be administered as clinically
indicated and the patient will be withdrawn from study participation.
Special Instructions: Currently Not Provided
Keywords:
Antiangiogenic
Breast Carcinoma
Lung Carcinoma
Renal Cell Carcinoma
Sarcoma
Recruitment Keyword(s):
Tumor
Condition(s):
Kidney Cancer
Lung Carcinoma
Sarcomas
Investigational Drug(s):
IL-12/IL-2 Combinations
Investigational Device(s):
None
Intervention(s):
None
Supporting Site:
N/A
Contact(s):
Cynthia Donovan, R.N.
National Institutes of Health
Building 10
Room 13N240
10 Center Drive
Bethesda, Maryland 20892
Phone: (301) 402-8899
Fax: (301) 402-0575
Electronic Address: Not Specified
- Citation(s):
- Selective
in vitro growth of T lymphocytes from normal human bone marrows
- Functional
and morphologic characterization of human T cells continuously grown in
vitro
- Interleukin-2:
its biology and clinical application in patients with cancer
Active Accrual, Protocols Recruiting New Patients
If you have:
- Questions about participating in a study, please contact the
Patient Recruitment and Public Liaison Office, CC. - Technical questions regarding the Clinical Center web site,
please contact the
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