Phase I Study Of SS1(dsFv)-PE38 Anti-Mesothelin Immunotoxin In Advanced Malignancies: I.V. Infusion QOD Dosing
18 Years
N/A
Both
Cervical Cancer, Fallopian Tube Cancer, Head and Neck Cancer, Lung Cancer, Malignant Mesothelioma, Ovarian Cancer, Pancreatic Cancer, Primary Peritoneal Cavity Cancer
Trial Information
Phase I Study Of SS1(dsFv)-PE38 Anti-Mesothelin Immunotoxin In Advanced Malignancies: I.V. Infusion QOD Dosing
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Raffit Hassan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
CDR0000316451
NCT ID:
NCT00066651
Start Date:
July 2003
Completion Date:
Related Keywords:
- Cervical Cancer
- Fallopian Tube Cancer
- Head and Neck Cancer
- Lung Cancer
- Malignant Mesothelioma
- Ovarian Cancer
- Pancreatic Cancer
- Primary Peritoneal Cavity Cancer
- 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
- Uterine Cervical Neoplasms
- Head and Neck Neoplasms
- Lung Neoplasms
- Mesothelioma
- Ovarian Neoplasms
- Pancreatic Neoplasms
- Peritoneal Neoplasms
- Fallopian Tube Neoplasms
Name | Location |
|---|---|
| Comprehensive Cancer Center at Wake Forest University | Winston-Salem, North Carolina 27157-1082 |
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
