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SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01445392
Recruitment Status : Terminated
First Posted : October 3, 2011
Last Update Posted : August 3, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


Standard therapy for mesothelioma is a combination of the drugs pemetrexed and cisplatin. However, the benefits of this treatment are limited, and in most treated patients the disease continues to worsen.

SS1(dsFV)PE38 is a genetically engineered drug. It contains an antibody that binds to a certain protein on mesothelioma cells and a toxin (type of poison) made from a product of a bacterium called Pseudomonas aeruginosa. It is hoped that the antibody will attach to the cancer cells, allowing the toxin to enter and kill the cells.


To find out if SS1(dsFV)PE38, together with pemetrexed and cisplatin is safe and tolerable in patients with mesothelioma.

To determine the maximum tolerated dose of SS1(dsFV)PE38 (the highest dose that does not cause unacceptable side effects).

To see if SS1(dsFV)PE38 given with pemetrexed and cisplatin has any effect on patients tumors.

To learn how the body breaks down SS1(dsFV)PE38.


Patients 18 years of age and older with epithelial pleural mesothelioma whose disease cannot be cured with surgery, and have not had prior treatment with chemotherapy.


Treatment with pemetrexed, cisplatin and SS1(dsFV)PE38 in two 21-day cycles as follows:

  • Day 1 - Intravenous (through a vein) infusions of pemetrexed and cisplatin.
  • Days 1 and 2 - Intravenous solution to prevent dehydration that might occur with SS1(dsFV)PE38.
  • Days 1, 3 and 5 Intravenous infusion of SS1(dsFV)PE38. Small groups (3 to 6) of patients are given SS1(dsFV)PE38 at a certain dose level. If the first group experiences no significant side effects, the next group a higher dose. This continues in succeeding groups until the maximum tolerated study dose (highest dose that patients can be given safely) is determined.

Continuing standard treatment with additional cycles of pemetrexed and cisplatin.

Evaluations during the treatment period:

  • Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
  • Questions about medications and side effects.
  • Blood and urine tests.
  • Disease evaluation with CT, chest X-ray, and possibly PET scans, lung function tests, pulse oximetry, performance of daily activities and quality-of-life questionnaires.

Post-treatment evaluations:

  • Clinic visits at months 1, 3, 6, 12, 15, 18 and 21 for physical examination and disease assessment.
  • End-of-study visit for blood tests, vital signs and weight measurements, disease assessment, electrocardiogram, pregnancy test for women who can become pregnant

Condition or disease Intervention/treatment Phase
Mesothelioma Biological: Multicycle SS1P Drug: Pemetrexed Drug: Cisplatin Biological: Single cycle SS1P Phase 1

Detailed Description:


SS1P (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 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.


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.


Subjects with histologically confirmed epithelial pleural mesothelioma.

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


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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : November 14, 2007
Actual Primary Completion Date : January 31, 2014
Actual Study Completion Date : October 3, 2016

Arm Intervention/treatment
Experimental: 1
Multi-cycle cohort
Biological: Multicycle SS1P
Assigned dose level of SS1(dsFv)PE38 on days 1, 3 & 5 of a 21 day cycle for 2 cycles

Drug: Pemetrexed
500 mg/m^2 on day 1 of each 21 day cycle until disease progression

Drug: Cisplatin
75 mg/m^2 on day 1 of each 21 day cycle until disease progression

Experimental: 2
Single cycle cohort
Drug: Pemetrexed
500 mg/m^2 on day 1 of each 21 day cycle until disease progression

Drug: Cisplatin
75 mg/m^2 on day 1 of each 21 day cycle until disease progression

Biological: Single cycle SS1P
Patients 1 - 3 of single cycle cohort. 45 mcg/kg of SS1(dsFv)PE38 on 4 or 5 days (depending on dose level) of cycle 1 only.

Primary Outcome Measures :
  1. Safety and MTD [ Time Frame: 30 days after last dose ]
    list of adverse events and highest dose at which fewer than 2 subjects experienced DLT

  2. Best overall response [ Time Frame: Assessed every 42 days until disease progression ]
    proportion of subjects experiencing complete response, partial response or stable disease as a best overall response

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01445392

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Raffit Hassan, M.D. National Cancer Institute (NCI)
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT01445392    
Obsolete Identifiers: NCT00575770
Other Study ID Numbers: 080026
First Posted: October 3, 2011    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 1, 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Recombinant Immunotoxin
Monoclonal Antibody
Pseudomonas Exotoxin
Targeted Therapy
Pleural Mesothelioma
Epithelial Pleural Mesothelioma
Additional relevant MeSH terms:
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Mesothelioma, Malignant
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases
Antibodies, Monoclonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Immunologic Factors
Physiological Effects of Drugs