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

Phase 1
18 Years
Not Enrolling
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

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Trial Information

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


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

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

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.

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

Type of Study:


Study Design:

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

Outcome 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

Outcome Time Frame:

Up to 21 days

Safety Issue:


Principal Investigator

William Carson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

November 2001

Completion Date:

Related Keywords:

  • 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
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Stomach Neoplasms
  • Small Cell Lung Carcinoma
  • Adenoma
  • Breast Neoplasms, Male
  • Endometrial Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms



Ohio State University Medical Center Columbus, Ohio  43210