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

NCT01445392 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 08002608-C-0026
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Mesothelioma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Safety and MTD

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

  30 days after last dose

• Best overall response

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

  Assessed every 42 days until disease progression

Study Arms (2)

1

EXPERIMENTAL

Multi-cycle cohort

Biological: Multicycle SS1P; Drug: Pemetrexed; Drug: Cisplatin

2

EXPERIMENTAL

Single cycle cohort

Drug: Pemetrexed; Drug: Cisplatin; Biological: Single cycle SS1P

Interventions

Multicycle SS1P BIOLOGICAL

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

1

Pemetrexed DRUG

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

1; 2

Cisplatin DRUG

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

1; 2

Single cycle SS1P BIOLOGICAL

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.

2

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Chang K, Pastan I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40. doi: 10.1073/pnas.93.1.136.

  PMID: 8552591 BACKGROUND

• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.

  PMID: 1244564 BACKGROUND

• Hassan R, Kreitman RJ, Pastan I, Willingham MC. Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol. 2005 Sep;13(3):243-7. doi: 10.1097/01.pai.00000141545.36485.d6.

  PMID: 16082249 BACKGROUND

MeSH Terms

Conditions

Mesothelioma; Mesothelioma, Malignant

Interventions

Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Raffit Hassan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 3, 2011
• Study Start: November 14, 2007
• Primary Completion: January 31, 2014
• Study Completion: October 3, 2016
• Last Updated: August 3, 2018

Record last verified: 2018-08-01

Locations

US (1)