Clinical trial NCT00028535: Interleukin-12, Paclitaxel, and Trastuzumab in Treating Patients With Solid Tumors
Official title: Phase I Trial of Interleukin-12 in Combination With Paclitaxel Plus Herceptin in Patients With Her2-positive Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Male Breast Cancer
Recurrent Breast Cancer
Recurrent Endometrial Carcinoma
Recurrent Gastric Cancer
Recurrent Non-small Cell Lung Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Small Cell Lung Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 18
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 I trial to study the effectiveness of interleukin-12, paclitaxel, and trastuzumab in treating patients who have solid tumors. 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. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining interleukin-12, chemotherapy, and monoclonal antibody therapy may kill more tumor cells.

Detailed description: OBJECTIVES:

I. Determine the maximum tolerated dose of interleukin-12 when given in combination with paclitaxel and trastuzumab (Herceptin®) in patients with HER2/neu-overexpressing malignancies.

II. Determine the response rate and time to progression in patients treated with this regimen.

III. Determine the anti-tumor effect of this regimen in these patients.

OUTLINE: This is a dose-escalation study of interleukin-12.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 1 of course 1. Beginning with course 2, patients receive trastuzumab and paclitaxel as in course 1 and interleukin-12 subcutaneously on days 2, 5, 9, 12, 16, and 19. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

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

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed HER2/neu-overexpressing (2+ or 3+) malignancy by any standardized assay (fluorescence in-situ hybridization allowed)
* Measurable or evaluable disease
* Failed standard curative therapy
* No brain or CNS metastasis
* Hormone receptor status:

  * Not specified
* Male or female
* Performance status - Karnofsky 70-100%
* At least 6 months
* Absolute neutrophil count at least 1,500/mm\^3
* Hemoglobin at least 8 g/dL (transfusion or epoetin alfa allowed)
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST and ALT no greater than 3.0 times ULN
* Hepatitis B surface antigen negative
* Creatinine no greater than 1.5 times ULN
* Calcium no greater than 11 mg/dL (calcium-lowering agents allowed)
* No active or unstable cardiovascular disease
* No cardiac disease requiring drug or device intervention
* No coronary artery disease
* No congestive heart failure
* Cardiac ejection fraction normal by echocardiogram or MUGA scan
* No significant peripheral neuropathy
* No significant CNS disease
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No serious concurrent infection requiring IV antibiotic therapy
* No clinically significant autoimmune disease (e.g., rheumatoid arthritis)
* No clinically significant gastrointestinal bleeding
* No uncontrolled peptic ulcer disease
* No inflammatory bowel disease
* No other major illness that would preclude study participation
* No other concurrent malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix
* No prior interleukin-12
* No prior trastuzumab (Herceptin®)
* At least 3 weeks since prior chemotherapy
* At least 3 weeks since prior hormonal therapy
* No concurrent systemic corticosteroids
* At least 3 weeks since prior radiotherapy
* At least 3 weeks since prior surgery
* At least 3 weeks since prior investigational drug

Primary outcomes:
measure: MTD of IL-12, defined as the dose level one level beneath that dose at which 2 or more of 6 patients showed DLT, based on the NCI CTC version 2.0
timeFrame: Up to 21 days
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: William Carson
role: PRINCIPAL_INVESTIGATOR
References: