Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00066651

Purpose

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be effective in treating advanced solid tumors.

PURPOSE: This phase I trial is studying the side effects and best dose of immunotoxin therapy in treating patients with recurrent unresectable advanced solid tumors.

Condition	Intervention	Phase
Cervical Cancer Fallopian Tube Cancer Head and Neck Cancer Lung Cancer Malignant Mesothelioma Ovarian Cancer Pancreatic Cancer Primary Peritoneal Cavity Cancer	Biological: SS1(dsFv)-PE38 immunotoxin	Phase I

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study Of SS1(dsFv)-PE38 Anti-Mesothelin Immunotoxin In Advanced Malignancies: I.V. Infusion QOD Dosing

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cervical Cancer Head and Neck Cancer Lung Cancer Mesothelioma Ovarian Cancer Pancreatic Cancer Sarcoidosis

U.S. FDA Resources

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

Study Start Date:

July 2003

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of SS1(dsFv)-PE38 immunotoxin in patients with advanced mesothelin-expressing malignancies.

Secondary

Determine the toxic effects of this drug in these patients.
Determine the plasma pharmacokinetics of this drug in these patients.
Determine the response in patients treated with this drug.
Correlate the induction of antibody against this drug with its pharmacokinetics in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive a test dose of SS1(dsFv)-PE38 immunotoxin IV over 1-2 minutes on day 1 followed by SS1(dsFv)-PE38 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SS1(dsFv)-PE38 immunotoxin 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.

PROJECTED ACCRUAL: A total of 3-15 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed advanced malignancy of 1 of the following types:
- Ovarian cancer
  - All nonmucinous epithelial histologies are eligible
- Primary peritoneal cavity cancer
- Fallopian tube cancer
- Malignant mesothelioma
  - No sarcomatous histology
- Pancreatic cancer
- Squamous cell cancer (SCC) of the lung
- SCC of the cervix
- SCC of the head and neck
Recurrent unresectable disease, meeting 1 of the following criteria:
- Previously treated with definitive standard therapy
- Patient refused prior standard therapy
Initial or recurrent tumor positive (at least 30% of tumor cells) for mesothelin by immunohistochemistry* NOTE: *Immunohistochemical evaluation not required for patients with pancreatic cancer
Measurable or evaluable disease
No clinically significant pericardial effusion
No known CNS or spinal cord involvement by tumor

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

At least 12 weeks

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 75,000/mm^3

Hepatic

Bilirubin no greater than upper limit of normal (ULN)
AST and ALT no greater than 2.5 times ULN
Albumin at least 3.0 g/dL
Hepatitis B and C negative
- Seropositive allowed if clinically asymptomatic
except if clinically asymptomatic and bilirubin and AST and ALT meet the outlined criteria

Renal

Creatinine no greater than ULN
Calcium no greater than ULN

Cardiovascular

No New York Heart Association class II-IV cardiovascular disease

Pulmonary

Oxygen saturation at least 93% on room air
DLCO at least 50% of predicted*
Total lung capacity and vital capacity at least 50% of predicted*
FEV_1 at least 50% of predicted* NOTE: *For patients with pleural mesothelioma and as clinically indicated

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No infection requiring parenteral antibiotics
No HIV infection
Serum neutralizing activity to SS1(dsFv)-PE38 immunotoxin (at 200 ng/mL) no greater than 75%

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

At least 4 weeks since prior therapy and recovered
No other concurrent antitumor therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066651

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, North Carolina
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1096

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Raffit Hassan, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

Feautured trial article This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00066651 History of Changes
Obsolete Identifiers:	NCT00065481
Other Study ID Numbers:	CDR0000316451, NCI-03-C-0243, NCI-6221, NCI-SS1PE-002
Study First Received:	August 6, 2003
Last Updated:	April 23, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

ovarian carcinosarcoma
ovarian clear cell cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian serous cystadenocarcinoma
ovarian undifferentiated adenocarcinoma
recurrent ovarian epithelial cancer
Brenner tumor
primary peritoneal cavity cancer
fallopian tube cancer
epithelial mesothelioma
recurrent malignant mesothelioma
recurrent pancreatic cancer

cervical squamous cell carcinoma
recurrent cervical cancer
recurrent non-small cell lung cancer
squamous cell lung cancer
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent metastatic squamous neck cancer with occult primary
recurrent salivary gland cancer
salivary gland squamous cell carcinoma
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the nasopharynx

Additional relevant MeSH terms:

Uterine Cervical Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Mesothelioma
Ovarian Neoplasms
Pancreatic Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases

Genital Diseases, Female
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Endocrine System Diseases
Gonadal Disorders
Digestive System Neoplasms

ClinicalTrials.gov processed this record on February 12, 2012