Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Immunotoxin Therapy in Treating Patients With Advanced Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI NCI-01-C-0011 6249, NCI-6249, NCT00006981

Objectives

Primary

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

Secondary

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

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignancy, including one of the following:
  • Malignant mesothelioma
  • Ovarian epithelial carcinoma (mucinous or nonmucinous), including primary peritoneal or fallopian tube carcinoma
    • Tumors that may have originated in the bowel (e.g., appendiceal carcinoma) and involve the ovary
    • Ovarian cancers of other histology are eligible provided they express mesothelin
  • 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

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

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/mm³
• Platelet count at least 75,000/mm³

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 (SO₂) 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

Expected Enrollment

A total of 30 patients will be accrued for this study.

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.

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.

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Robert Kreitman, MD, Protocol chair		Ph: 301-496-6947 Email: kreitmar@mail.nih.gov

Registry Information
Official Title		Phase I Study Of SS1(dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies: Continuous Infusion X 10 Days
Trial Start Date		2000-12-11
Registered in ClinicalTrials.gov		NCT00006981
Date Submitted to PDQ		2000-11-01
Information Last Verified		2005-05-05