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

Recurrent Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028535
• Other study ID #: NCI-2012-01407
• Secondary ID: 1999C0326OSU-016
• Status: Completed
• Phase: Phase 1
• First received: January 4, 2002
• Last updated: June 3, 2013
• Start date: November 2001

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Carcinoma, Non-Small-Cell Lung
• Endometrial Neoplasms
• Lung Neoplasms
• Male Breast Cancer
• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms
• Recurrent Breast Cancer
• Recurrent Endometrial Carcinoma
• Recurrent Gastric Cancer
• Recurrent Non-small Cell Lung Cancer
• Recurrent Ovarian Epithelial Cancer
• Recurrent Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Biological:
• trastuzumab
Given IV

Drug:
• paclitaxel
Given IV

Biological:
• recombinant interleukin-12
Given SC

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes