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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Endometrial Carcinoma; Male Breast Cancer; Recurrent Small Cell Lung Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Gastric Cancer; Recurrent Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: paclitaxel; Biological: trastuzumab; Biological: recombinant interleukin-12

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: William Carson, Ohio State University

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (ACTUAL): February 1, 2009

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Lung Neoplasms; Recurrence; Endometrial Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Ovarian Epithelial; Breast Neoplasms, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Paclitaxel; Trastuzumab; Interleukin-12
• Other Study ID Numbers: NCI-2012-01407; U01CA076576 (U.S. NIH Grant/Contract); 1999C0326; OSU-0167; NCI-84; OSU-99H0326; CDR0000069102