Immunotoxin Therapy in Treating Patients With Advanced Cancer

Lung Cancer Clinical Trial

Official title:

Phase I Study Of SS1(dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies: Continuous Infusion X 10 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006981
• Other study ID #: CDR0000068351
• Secondary ID: NCI-01-C-0011NCI
• Status: Completed
• Phase: Phase 1
• First received: December 6, 2000
• Last updated: April 29, 2015
• Start date: December 2000

Study information

• Verified date: May 2005
• 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 an effective treatment for advanced cancer.

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

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.

Other known NCT identifiers

• NCT00006416

Recruitment information / eligibility

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

Eligibility

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

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

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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.

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. — View Citation