Combination Therapy of Interleukin-12 and Interleukin-2 to Treat Advanced Cancer

NCT00005655 | Terminated Phase 1

• 2 other identifiers: 00012100-C-0121
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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. ...

Conditions

Kidney Neoplasm; Lung Neoplasm; Sarcoma; Breast Neoplasm

Keywords

Gene Expression; Neovascularization; antiangiogenic therapy; immunomodulatory therapy; Immunotherapy; Tumor

Outcome Measures

Primary Outcomes (1)

• MTD and DLTof IL-12 in combination with IL-2

  1 month

Study Arms (1)

1

EXPERIMENTAL

rhIL-12 in combination with rhIL-2

Biological: rh IL-12; Biological: rh IL-2

Interventions

rh IL-12 BIOLOGICAL

rhIL-12 will be administered intravenously on days 2, 4, 6, 10, 12 and 14 of each cycle.

1

rh IL-2 BIOLOGICAL

rhIL-2 will be administered intravenously every 8 hours x 3 doses on days 1 and 9 of each cycle.

1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 cancer will have received sunitinib or sorefinib or refused this option.
• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007-8. doi: 10.1126/science.181845.

  PMID: 181845 BACKGROUND

• Ruscetti FW, Morgan DA, Gallo RC. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol. 1977 Jul;119(1):131-8.

  PMID: 141483 BACKGROUND

• Rubin JT. Interleukin-2: its biology and clinical application in patients with cancer. Cancer Invest. 1993;11(4):460-72. doi: 10.3109/07357909309018878. No abstract available.

  PMID: 8324650 BACKGROUND

MeSH Terms

Conditions

Kidney Neoplasms; Lung Neoplasms; Sarcoma; Breast Neoplasms; Neovascularization, Pathologic; Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas A Waldmann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 4, 2000
• First Posted: May 5, 2000
• Study Start: April 28, 2000
• Primary Completion: October 6, 2010
• Study Completion: March 2, 2017
• Last Updated: December 17, 2019

Record last verified: 2017-03-02

Locations

US (1)