Clinical trial NCT00004074: Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu
Official title: A Phase I Trial of Herceptin and Interleukin-12
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-10-29
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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 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

Primary outcomes:
measure: 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)
timeFrame: Up to 52 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: William Carson
role: PRINCIPAL_INVESTIGATOR
References: