Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors

Lung Cancer Clinical Trial

Official title:

Phase I Study Of SS1(dsFv)-PE38 Anti-Mesothelin Immunotoxin In Advanced Malignancies: I.V. Infusion QOD Dosing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066651
• Other study ID #: CDR0000316451
• Secondary ID: NCI-03-C-0243NCI
• Status: Completed
• Phase: Phase 1
• First received: August 6, 2003
• Last updated: April 29, 2015
• Start date: July 2003

Study information

• Verified date: February 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00065481

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Cancer
• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma
• Ovarian Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• SS1(dsFv)-PE38 immunotoxin

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,