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A Phase 1, Single Center, Dose-Escalation Study of SS1(dsFv)PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Mesothelioma

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Trial Information

A Phase 1, Single Center, Dose-Escalation Study of SS1(dsFv)PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma


Background:

SS1(dsFV)PE38, is a recombinant immunotoxin targeting the tumor antigen mesothelin that is
highly expressed in malignant mesothelioma. The maximum tolerated dose (MTD) of
SS1(dsFV)PE38 has been established in a phase I study.

Combination therapy with pemetrexed plus cisplatin is the standard first line therapy for
malignant mesothelioma, but results in a median overall survival of only 12.1 months.

Combination of SS1(dsFV)PE38 with pemetrexed plus cisplatin could result in improved
outcomes for patients with mesothelioma.

Objectives:

To determine the MTD of SS1(dsFV)PE38 that can be safely administered in combination with
pemetrexed plus cisplatin in patients with mesothelioma.

To characterize the toxicity profile of SS1(dsFV)PE38.

To study the pharmacokinetics of SS1(dsFV)PE388.

To observe anti-tumor activity, if any of SS1(dsFV)PE38 in combination with pemetrexed plus
cisplatin.

Eligibility:

Subjects with histologically confirmed epithelial pleural mesothelioma.

No prior radiotherapy (except palliative extra-thoracic localized radiotherapy),systemic
chemotherapy or biologic therapy for pleural mesothelioma.

Design:

This is a phase I dose-escalation study of SS1(dsFV)PE38 in combination with pemetrexed plus
cisplatin.

The dose of pemetrexed plus cisplatin will be the standard dose approved for malignant
mesothelioma. The dose of SS1(dsFV)PE38 will be escalated to find the safe dose in
combination with pemetrexed plus cisplatin.

SS1(dsFV)PE38 will be administered concurrently with pemetrexed plus cisplatin in cycles one
and two, and subjects will receive additional cycles of pemetrexed and cisplatin as per
standard practice.

Patients will be assessed for response every 6 weeks.

An additional Single Cycle of SS1(dsFv)PE38 Cohort will involve up to 16 patients

who will receive SS1(dsFv)PE38 administered for four or five doses during the first cycle

concurrently with pemetrexed and cisplatin; subjects in this cohort will receive additional

cycles of pemetrexed and cisplatin as per standard practice

Inclusion Criteria


- INCLUSION CRITERIA:

Subjects must meet all of the following criteria to be eligible to participate in the
study:

Subjects must have histologically confirmed epithelial or biphasic pleural mesothelioma
not amenable to potentially curative surgical resection. However, patients with biphasic
tumors that have a predominantly sarcomatoid component will be excluded.

Measurable disease

Subjects must be greater than or equal to 18 years old

Karnofsky Performance Status (KPS) of greater than or equal to 70

Life expectancy of greater than 3 months, as assessed by the principal investigator.

Adequate organ function with:Hepatic function: serum transaminases (either ALT or AST) or
bilirubin, less than or equal to Grade 1, unless due to cancer or Gilbert's disease; less
than or equal to Grade 2, if due to cancer

Renal function: serum creatinine clearance greater than or equal to 60mL/min as estimated
by Cockroft-Gault formula.

Bone marrow function: ANC of at least 1,500/mm (3), Platelet count at least 100,000/mm (3)

Pulmonary Function: FEV (1) greater than or equal to 50 percent of predicted value
(post-pleural drainage and bronchodilation if these are indicated)

Must be able to understand and sign informed consent

Female and male subjects agree to use an approved method of contraception during the study

EXCLUSION CRITERIA:

Subjects must not be pregnant or breast feeding

Prior radiotherapy (except palliative extra-thoracic localized radiotherapy) or biologic
therapy for malignant pleural mesothelioma within 4 weeks

Prior systemic chemotherapy for malignant pleural mesothelioma

Documented and ongoing central nervous system involvement with their malignant disease
(history of CNS involvement is not an exclusion criterion but the CNS metastases should
have been adequately treated (radiation or surgical resection) and subjects are free from
symptoms for 3 months off steroids).

Clinically significant heart disease (New York Heart Association Class III or IV)

Active bacterial or fungal infection.

Baseline coagulopathy greater than or equal to Grade 3 unless due to anticoagulant therapy

Surgery or pleurodesis within 2 weeks

HIV positive serology (due to increased risk of severe infection and unknown interaction
of SS1(dsFv)PE38 with antiretroviral drugs)

Hepatitis B surface antigen positivity

Subjects with other (non-mesothelioma) cancers who meet eligibility criteria and have had
less than 5 years of disease-free survival will be considered on a case-by-case basis

Uncontrolled, symptomatic, intercurrent illness including but not limited to: infections
requiring systemic antibiotics, unstable angina pectoris, cardiac arrhythmia, psychiatric
illness, or social situations that would limit compliance with study requirements.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Est MTD, study pharmacokinetics, observe anti-tumor response

Principal Investigator

Raffit Hassan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

080026

NCT ID:

NCT01445392

Start Date:

November 2007

Completion Date:

Related Keywords:

  • Mesothelioma
  • Recombinant Immunotoxin
  • Monoclonal Antibody
  • Pseudomonas Exotoxin
  • Targeted Therapy
  • Pleural Mesothelioma
  • Mesothelioma
  • Epithelial Pleural Mesothelioma
  • Mesothelioma

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892
University of Chicago Medical CenterChicago, Illinois  60637