Interleukin-12, Paclitaxel, and Trastuzumab in Treating Patients With Solid Tumors

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00028535

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: trastuzumab Drug: paclitaxel Biological: recombinant interleukin-12	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of interleukin-12 when given in combination with paclitaxel and trastuzumab (Herceptin®) in patients with HER2/neu-overexpressing malignancies.
Determine the response rate and time to progression in patients treated with this regimen.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Trial of Interleukin-12 in Combination With Paclitaxel Plus Herceptin in Patients With Her2-positive Malignancies

Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I 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.	Biological: trastuzumab Given IV Other Names: anti-c-erB-2 Herceptin MOAB HER2 Drug: paclitaxel Given IV Other Names: Anzatax Asotax TAX Taxol Biological: recombinant interleukin-12 Given SC Other Names: cytotoxic lymphocyte maturation factor IL-12 interleukin-12 natural killer cell stimulatory factor Ro 24-7472

Arm

Intervention/Treatment

Experimental: Arm I

Biological: trastuzumab

Given IV

Other Names:

anti-c-erB-2

Herceptin

MOAB HER2

Drug: paclitaxel

Given IV

Other Names:

Anzatax

Asotax

TAX

Taxol

Biological: recombinant interleukin-12

Given SC

Other Names:

cytotoxic lymphocyte maturation factor

IL-12

interleukin-12

natural killer cell stimulatory factor

Ro 24-7472

Outcome Measures

Primary Outcome Measures

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 [Up to 21 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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