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Assigned dose level of SS1(dsFv)PE38 on days 1, 3 \&amp; 5 of a 21 day cycle for 2 cycles

Multicycle SS1P

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

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

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.

Single cycle SS1P

Raffit Hassan, M.D.

Background:

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.

Objectives:

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.

Eligibility:

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.

Design:

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

Background:

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.

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 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

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

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

list of adverse events and highest dose at which fewer than 2 subjects experienced DLT

proportion of subjects experiencing complete response, partial response or stable disease as a best overall response

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma	NCT01445392	Mesothelioma	Multicycle SS1P Pemetrexed Cisplatin Single cycle SS...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma	NCT01445392	Mesothelioma	Multicycle SS1P Pemetrexed Cisplatin Single cycle SS...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)

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