Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00066651

Last Updated: 2015-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31

Brief 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.

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.

Conditions

Cervical Cancer; Fallopian Tube Cancer; Head and Neck Cancer; Lung Cancer; Malignant Mesothelioma; Ovarian Cancer; Pancreatic Cancer; Primary Peritoneal Cavity Cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

SS1(dsFv)-PE38 immunotoxin

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Raffit Hassan, MD

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

NCI-03-C-0243

Identifier Type: -

Identifier Source: secondary_id

NCI-6221

Identifier Type: -

Identifier Source: secondary_id

NCI-SS1PE-002

Identifier Type: -

Identifier Source: secondary_id

CDR0000316451

Identifier Type: -

Identifier Source: org_study_id

NCT00065481

Identifier Type: -

Identifier Source: nct_alias