Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors

April 29, 2015 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Comprehensive Cancer Center at Wake Forest University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Raffit Hassan, MD, National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Study Registration Dates

First Submitted

August 6, 2003

First Submitted That Met QC Criteria

August 6, 2003

First Posted (ESTIMATE)

August 7, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

April 30, 2015

Last Update Submitted That Met QC Criteria

April 29, 2015

Last Verified

February 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000316451
  • NCI-03-C-0243
  • NCI-6221
  • NCI-SS1PE-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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