Immunotoxin Therapy in Treating Patients With Advanced Cancer

NCT ID: NCT00006981

Last Updated: 2015-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-12-31

Brief Summary

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be an effective treatment for advanced cancer.

PURPOSE: Phase I trial to study the effectiveness of immunotoxins in treating patients who have advanced cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and toxic effects of SS1(dsFv)-PE38 immunotoxin in patients with advanced malignancies that express mesothelin.

Secondary

• Determine the response in patients treated with this drug.
• Determine the plasma pharmacokinetics of this drug in these patients.

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

Patients receive SS1(dsFv)-PE38 immunotoxin IV continuously on days 1-10. Treatment repeats every 4 weeks for a maximum of 4 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 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 30 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

• Pancreatic cancer
• Squamous cell lung cancer
• Squamous cell cancer of the head and neck
• Squamous cell cancer of the cervix
• Recurrent unresectable disease after prior standard anticancer therapy that was expected to prolong survival and improve quality of life OR unwilling to receive standard anticancer therapy
• At least 30% of initial or recurrent tumor cells positive (at least 1+) for mesothelin by immunohistochemistry
• Measurable or evaluable disease
• No known CNS or spinal cord involvement
• No clinically significant pericardial effusion

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/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

Renal:

• Creatinine no greater than ULN OR
• Creatinine no greater than 2.0 mg/dL if creatinine clearance at least 50 mL/min
• Calcium no greater than ULN

Cardiovascular:

• No New York Heart Association class II-IV heart disease

Pulmonary:

• Oxygen saturation (SO_2) more than 92% on room air

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No detectable antibody to SS1(dsFv)-PE38
• No infection requiring parenteral antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior hematopoietic growth factor therapy

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 4 weeks since any prior antitumor 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

Robert Kreitman, MD

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

References

Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin Cancer Res. 2009 Aug 15;15(16):5274-9. doi: 10.1158/1078-0432.CCR-09-0062. Epub 2009 Aug 11.

Reference Type: RESULT

PMID: 19671873 (View on PubMed)

Hassan R, Kreitman R, Strauss L, et al.: SS1(dsFv)-PE38 anti-mesothelin immunotoxin in advanced malignancies: phase I and pharmacokinetic study of alternate-day infusion. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-113, 2002.

Reference Type: RESULT

Kreitman R, Squires D, O'Hagan D, et al.: SS1(dsFv)-PE38 anti-mesothelin immunotoxin in advanced malignancies: phase I study of continuous infusion. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1896, 2002.

Reference Type: RESULT

Other Identifiers

NCI-01-C-0011

Identifier Type: -

Identifier Source: secondary_id

NCI-6249

Identifier Type: -

Identifier Source: secondary_id

CDR0000068351

Identifier Type: -

Identifier Source: org_study_id

NCT00006416

Identifier Type: -

Identifier Source: nct_alias