Clinical trial NCT00026143: Interleukin-12 and Interferon Alfa in Treating Patients With Metastatic Malignant Melanoma
Official title: Phase II Trial of Interleukin-12 (NSC #672423, IND #6798) Followed by Interferon Alfa-2B in Patients With Metastatic Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Melanoma
Stage IV Melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II trial to study the effectiveness of combining interleukin-12 and interferon alfa in treating patients who have metastatic malignant melanoma. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of the cancer cells. Combining interleukin-12 and interferon alfa may kill more tumor cells.

Detailed description: PRIMARY OBJECTIVES:

I. To estimate the clinical response rates in patients with metastatic malignant melanoma treated with rhIL-12 and interferon alfa-2b.

II. To estimate the progression-free survival in patients with metastatic malignant melanoma treated with rhIL-12 and interferon alfa-2b.

SECONDARY OBJECTIVES:

I. To measure serum levels of interferon-gamma. II. To measure levels of JAK-STAT signaling intermediates in patient PBMCs and tumor samples.

III. To analyze interferon-alpha-induced STAT signaling in patient PBMCs. IV. To determine the expression of IFN-regulated genes in patient PBMCs and tumor tissues.

V. To determine the pattern of gene expression induced by treatment with IL-12 and interferon-alpha using DNA microarray techniques in patient PBMCs.

OUTLINE: This is a multicenter study.

Patients receive interleukin-12 IV over 5-15 seconds on day 1 and interferon alfa subcutaneously on days 2-6. Treatment repeats every 2 weeks in the absence of unacceptable toxicity. Patients are reassessed after 6 courses. Patients with a complete response receive 2 additional courses. Patients with a partial response or stable disease continue treatment in the absence of disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 1 year.

Eligibility criteria: Inclusion Criteria:

* Histological or cytological diagnosis of cutaneous melanoma and clinical evidence of distant, metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease
* Patients must have measurable disease; measurable disease is defined as the presence of at least one measurable lesion; if the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology; measurable lesions are defined as lesions that can be accurately measured in at least one dimension with the longest diameter \>= 20 mm using conventional techniques or \>= 10 mm with spiral CT scan

  * Lesions that are considered intrinsically non-measurable include the following:

    * Bone lesions;
    * Leptomeningeal disease;
    * Ascites;
    * Pleural/pericardial effusion;
    * Inflammatory breast disease;
    * Lymphangitis cutis/pulmonis;
    * Abdominal masses that are not confirmed and followed by imaging techniques;
    * Lytic lesions;
    * Lesions that are situated in a previously irradiated area
* No history of peripheral neuropathy, brain metastases or other central nervous system disease
* No history of/active autoimmune disease, hemolytic anemia or concurrent requirement for corticosteroids, including topical or inhaled
* No hepatitis BSAg, known HIV disease or other major active illness; patients with risk factors for HIV should be tested; patients with these illnesses are more likely to experience significant side effects from the study treatment
* No history of severe peptic ulcer disease or gastrointestinal bleeding unless there is objective evidence that the condition is inactive or resolved
* No uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection
* No chemotherapy, radiotherapy, or anti-hormonal therapy within three weeks prior to the initiation of therapy on this study
* No prior therapy with IL-12
* No prior therapy with IFN-alpha for metastatic disease (e.g., biochemotherapy); prior adjuvant therapy with IFN-a is acceptable as long as the patient remained disease-free for 12 months or longer following the last IFN-a treatment
* No prior cytokine therapy for metastatic disease (e.g., high-dose IL-2)
* No more than one prior chemotherapy regimen
* CTC (ECOG) performance status 0-1
* Non-pregnant, non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control; women of child-bearing age will undergo pregnancy testing
* ANC \>= 1500/μL
* Platelets \>= 100,000/μL
* Hemoglobin \> 9 g/dL (may be post transfusion or may receive EPO)
* U-HCG or Serum HCG Negative (if patient of child-bearing potential)

Primary outcomes:
measure: Response rate
timeFrame: Up to 2 years
measure: PFS
timeFrame: From registration until time of documented progression of disease or death from any cause, assessed up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Cancer and Leukemia Group B
state: Illinois
Study officials:
affiliation: Cancer and Leukemia Group B
name: William Carson
role: PRINCIPAL_INVESTIGATOR
References: