This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004074
First received: December 10, 1999
Last updated: February 27, 2013
Last verified: February 2013
  Purpose
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. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Phase I trial to study the effectiveness of interleukin-12 and trastuzumab in treating patients who have cancer that has high levels of HER2/neu and has not responded to previous therapy

Condition Intervention Phase
Advanced Adult Primary Liver Cancer Anaplastic Thyroid Cancer Bone Metastases Carcinoma of the Appendix Distal Urethral Cancer Fallopian Tube Cancer Gastrinoma Glucagonoma Inflammatory Breast Cancer Insulinoma Liver Metastases Localized Unresectable Adult Primary Liver Cancer Lung Metastases Male Breast Cancer Malignant Pericardial Effusion Malignant Pleural Effusion Metastatic Gastrointestinal Carcinoid Tumor Metastatic Parathyroid Cancer Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter Newly Diagnosed Carcinoma of Unknown Primary Occult Non-small Cell Lung Cancer Pancreatic Polypeptide Tumor Primary Peritoneal Cavity Cancer Proximal Urethral Cancer Pulmonary Carcinoid Tumor Recurrent Adenoid Cystic Carcinoma of the Oral Cavity Recurrent Adrenocortical Carcinoma Recurrent Adult Primary Liver Cancer Recurrent Anal Cancer Recurrent Bladder Cancer Recurrent Breast Cancer Recurrent Carcinoma of Unknown Primary Recurrent Cervical Cancer Recurrent Colon Cancer Recurrent Endometrial Carcinoma Recurrent Esophageal Cancer Recurrent Extrahepatic Bile Duct Cancer Recurrent Gallbladder Cancer Recurrent Gastric Cancer Recurrent Gastrointestinal Carcinoid Tumor Recurrent Islet Cell Carcinoma Recurrent Malignant Testicular Germ Cell Tumor Recurrent Mucoepidermoid Carcinoma of the Oral Cavity Recurrent Non-small Cell Lung Cancer Recurrent Ovarian Epithelial Cancer Recurrent Pancreatic Cancer Recurrent Parathyroid Cancer Recurrent Prostate Cancer Recurrent Rectal Cancer Recurrent Renal Cell Cancer Recurrent Salivary Gland Cancer Recurrent Small Intestine Cancer Recurrent Squamous Cell Carcinoma of the Larynx Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity Recurrent Squamous Cell Carcinoma of the Nasopharynx Recurrent Squamous Cell Carcinoma of the Oropharynx Recurrent Thyroid Cancer Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter Recurrent Urethral Cancer Recurrent Vaginal Cancer Recurrent Vulvar Cancer Skin Metastases Small Intestine Adenocarcinoma Somatostatinoma Stage III Adenoid Cystic Carcinoma of the Oral Cavity Stage III Adrenocortical Carcinoma Stage III Bladder Cancer Stage III Cervical Cancer Stage III Colon Cancer Stage III Endometrial Carcinoma Stage III Esophageal Cancer Stage III Follicular Thyroid Cancer Stage III Gastric Cancer Stage III Malignant Testicular Germ Cell Tumor Stage III Mucoepidermoid Carcinoma of the Oral Cavity Stage III Ovarian Epithelial Cancer Stage III Pancreatic Cancer Stage III Papillary Thyroid Cancer Stage III Prostate Cancer Stage III Rectal Cancer Stage III Renal Cell Cancer Stage III Salivary Gland Cancer Stage III Squamous Cell Carcinoma of the Larynx Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity Stage III Squamous Cell Carcinoma of the Nasopharynx Stage III Squamous Cell Carcinoma of the Oropharynx Stage III Vaginal Cancer Stage III Vulvar Cancer Stage IIIA Anal Cancer Stage IIIA Breast Cancer Stage IIIA Non-small Cell Lung Cancer Stage IIIB Anal Cancer Stage IIIB Breast Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Adenoid Cystic Carcinoma of the Oral Cavity Stage IV Adrenocortical Carcinoma Stage IV Anal Cancer Stage IV Bladder Cancer Stage IV Breast Cancer Stage IV Colon Cancer Stage IV Endometrial Carcinoma Stage IV Esophageal Cancer Stage IV Follicular Thyroid Cancer Stage IV Gastric Cancer Stage IV Mucoepidermoid Carcinoma of the Oral Cavity Stage IV Non-small Cell Lung Cancer Stage IV Ovarian Epithelial Cancer Stage IV Pancreatic Cancer Stage IV Papillary Thyroid Cancer Stage IV Prostate Cancer Stage IV Rectal Cancer Stage IV Renal Cell Cancer Stage IV Salivary Gland Cancer Stage IV Squamous Cell Carcinoma of the Larynx Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IV Squamous Cell Carcinoma of the Nasopharynx Stage IV Squamous Cell Carcinoma of the Oropharynx Stage IVA Cervical Cancer Stage IVA Vaginal Cancer Stage IVB Cervical Cancer Stage IVB Vaginal Cancer Stage IVB Vulvar Cancer Thyroid Gland Medullary Carcinoma Unresectable Extrahepatic Bile Duct Cancer Unresectable Gallbladder Cancer Urethral Cancer Associated With Invasive Bladder Cancer WDHA Syndrome Biological: recombinant interleukin-12 Biological: ABI-007/carboplatin/trastuzumab Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Herceptin and Interleukin-12

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 2.0 (CTCAE v2.0) [ Time Frame: Up to 52 weeks ]

Enrollment: 15
Study Start Date: August 1999
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (IL12 and trastuzumab)
Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks.
Biological: recombinant interleukin-12
Given IV
Other Names:
  • cytotoxic lymphocyte maturation factor
  • IL-12
  • interleukin-12
  • natural killer cell stimulatory factor
  • Ro 24-7472
Biological: ABI-007/carboplatin/trastuzumab
Given IV

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies.

II. Determine the safety of this regimen in these patients.

III. Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen.

IV. Characterize natural killer cytokine production in patients treated with this regimen.

V. Determine serum interferon gamma levels in patients treated with this regimen.

OUTLINE:

This is a dose escalation study of interleukin-12 (IL-12).

Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks.

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

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

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a histologically proven Her2 overexpressing malignancy as determined by any standardized assay currently in clinical use
  • Patients must have measurable or evaluable disease
  • The patient must have failed standard curative and/or palliative therapies for their disease
  • Life expectancy of at least 6 months
  • No concurrent malignancy other than non-melanoma skin carcinoma
  • Adequate hematopoietic, cardiac, renal, and hepatic function
  • Calculated creatinine clearance will be used to assess renal function
  • Karnofsky Performance Status index >= 70%
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; a woman of childbearing potential is defined as a female who is biologically capable of becoming pregnant
  • Normal cardiac ejection fraction by echocardiogram or MUGA (i.e., greater than OSU lower limit of normal)
  • Written signed informed consent; the patient must be aware that his/her disease is neoplastic in nature and willingly consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

Exclusion Criteria:

  • History of significant peripheral neuropathy or significant central nervous system disease
  • Brain or central nervous system metastasis at entry
  • Active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention; history of coronary artery disease or congestive heart failure
  • Pregnant or nursing women
  • Surgery, radiotherapy, chemotherapy, or hormonal therapy during the three weeks prior to the initiation of therapy
  • Exposure to any investigational drug within three weeks prior to the start of dosing
  • Concurrent use of systemic corticosteroids
  • Known seropositive for hepatitis B surface antigen
  • Known seropositive for HIV antibody
  • Serious concurrent infection requiring intravenous antibiotic therapy
  • Clinically significant autoimmune disease (e.g., rheumatoid arthritis)
  • Clinically significant gastrointestinal bleeding or uncontrolled peptic ulcer disease
  • History of inflammatory bowel disease
  • Any other major illness which, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study
  • Prior therapy with Herceptin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004074

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: William Carson Ohio State University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004074     History of Changes
Other Study ID Numbers: NCI-2012-01398
99H0185
U01CA076576 ( US NIH Grant/Contract Award Number )
CDR0000067282 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: December 10, 1999
Last Updated: February 27, 2013

Additional relevant MeSH terms:
Lung Neoplasms
Prostatic Neoplasms
Breast Neoplasms
Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Pancreatic Neoplasms
Stomach Neoplasms
Rectal Neoplasms
Liver Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Urinary Bladder Neoplasms
Esophageal Neoplasms
Colonic Neoplasms
Uterine Cervical Neoplasms
Laryngeal Neoplasms
Fallopian Tube Neoplasms
Thyroid Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Salivary Gland Neoplasms
Testicular Neoplasms
Anus Neoplasms
Gallbladder Neoplasms
Carcinoid Tumor
Neuroendocrine Tumors
Bile Duct Neoplasms
Breast Neoplasms, Male

ClinicalTrials.gov processed this record on June 28, 2017