Immunotoxin Therapy, Pemetrexed, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed by Surgery - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00575770

Purpose

RATIONALE: Immunotoxins can find tumor cells and kill them without harming normal cells. Drugs used in chemotherapy, such as pemetrexed and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with immunotoxin therapy may kill more malignant mesothelioma cells.

PURPOSE: This phase I trial is studying the side effects and best dose of immunotoxin therapy when given together with pemetrexed and cisplatin in treating patients with malignant pleural mesothelioma that cannot be removed by surgery.

Condition	Intervention	Phase
Malignant Mesothelioma	Biological: SS1(dsFv)-PE38 immunotoxin Drug: cisplatin Drug: pemetrexed disodium Other: immunoenzyme technique Other: immunohistochemistry staining method Other: pharmacological study Procedure: quality-of-life assessment	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control
Official Title:	A Phase I, Single Center, Dose-Escalation Study of SS1(dsFv)PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Mesothelioma Surgery

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of SS1(dsFv)-PE38 immunotoxin [ Designated as safety issue: Yes ]
Pharmacokinetics of SS1(dsFv)-PE38 immunotoxin [ Designated as safety issue: No ]
Antitumor response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measurement of antibody formation to drug and impact on pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	June 2007
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To estimate the maximum tolerated dose (MTD) of SS1(dsFv)-PE38 immunotoxin when administered with pemetrexed disodium and cisplatin and to establish a safe dose, based on the MTD for subsequent clinical testing (phase II recommended dose) in patients with unresectable malignant epithelial pleural mesothelioma.
To characterize the toxicity profile of SS1(dsFv)-PE38 immunotoxin.
To study the clinical pharmacology (i.e., pharmacokinetics) which may dictate modification of SS1(dsFv)-PE38 immunotoxin schedule and administration in future studies.
To observe antitumor activity, if any, especially in patients who receive SS1(dsFv)-PE38 immunotoxin at or near the MTD (or phase II recommended dose).

Secondary

To monitor antibody formation to SS1(dsFv)-PE38 immunotoxin and to assess the impact of these antibodies on SS1(dsFv)-PE38 immunotoxin pharmacokinetics (PKs).
To investigate the potential of soluble mesothelin levels to predict PKs or any therapeutic or toxic response.
To perform a pilot assessment of a validated quality of life instrument.

OUTLINE: This is a dose-escalation study of SS1(dsFv)-PE38 immunotoxin.

Patients receive SS1(dsFv)-PE38 immunotoxin IV over 30 minutes on days 1, 3, and 5, pemetrexed disodium IV over 10 minutes on day 1, and cisplatin IV over 2 hours on day 1 in courses 1 and 2. Beginning in course 3 and all subsequent courses, patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Monocytes are collected via apheresis after the first course to identify and remove T-cell epitopes in the immunotoxin protein for the design and production of less immunogenic immunotoxins in the future. Patients also undergo blood sample collection at baseline, before course 2, and day 21 of course 2 for laboratory and pharmacokinetic studies. Samples are analyzed for the presence of anti-SS1(dsFv)-PE38 immunotoxin antibodies using a study drug-specific immunoassay and for concentrations of circulating mesothelin using enzyme-linked immunosorbent assay. Tumor cells from archival paraffin block biopsy specimens are analyzed for expression of mesothelin via immunohistochemistry.

Patients complete a quality of life questionnaire (i.e., LCSS-MESO) at baseline, after course 2, and subsequently after every even course to assess symptoms including appetite loss, fatigue, cough, dyspnea, and pain.

After completion of study treatment, patients are followed up at 1, 3, 6, 12, 15, 18, 21, and 24 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed epithelial or biphasic pleural mesothelioma not amenable to potentially curative surgical resection
- Unresectable disease, defined as any 1 of the following:
  - Metastatic disease
  - Patient found at surgery not to be amenable to resection
  - Not to benefit from surgery due to extensive local disease or not a surgical candidate due to comorbid medical conditions as deemed by a qualified oncologist
No biphasic tumors that have a predominantly sarcomatoid component
Measurable disease
No documented and ongoing CNS involvement with malignant disease (history of CNS involvement is not an exclusion criterion)

PATIENT CHARACTERISTICS:

Inclusion criteria:

Karnofsky performance status 70-100%
Life expectancy > 3 months (assessed by the principal investigator)
ALT, AST, or bilirubin ≤ grade 1 (unless due to cancer or Gilbert disease) OR ≤ grade 2 (if due to cancer)
Serum creatinine clearance ≥ 60 mL/min
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
FEV_1 ≥ 50% of predicted value (post-pleural drainage and bronchodilation if these are indicated)
Must be able to understand and sign informed consent
Other (non-mesothelioma) cancers that meet eligibility criteria and have had less than 5 years of disease-free survival are considered on a case by case basis
May only be enrolled in this study once (i.e., no second time or later cohort re-enrollment)

Exclusion criteria:

Clinically significant heart disease (New York Heart Association class III or IV)
Active bacterial or fungal infection
Baseline coagulopathy ≥ grade 3 (unless due to anticoagulant therapy)
HIV-positive serology
Hepatitis B surface antigen positivity
Uncontrolled, symptomatic, intercurrent illness including, but not limited to, any of the following:
- Infections requiring systemic antibiotics
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior radiotherapy (except palliative extra-thoracic localized radiotherapy) or biologic therapy for malignant pleural mesothelioma
More than 2 weeks since prior surgery or pleurodesis
No prior systemic chemotherapy for malignant pleural mesothelioma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00575770

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Raffit Hassan, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000579640, NCI-08-C-0026, P07188, CAT-5001-1001
Study First Received:	December 15, 2007
Last Updated:	October 13, 2009
ClinicalTrials.gov Identifier:	NCT00575770 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

epithelial mesothelioma
advanced malignant mesothelioma
recurrent malignant mesothelioma

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Neoplasms, Mesothelial
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Folic Acid Antagonists
Immunotoxins

Pharmacologic Actions
Pemetrexed
Antibodies, Monoclonal
Neoplasms
Radiation-Sensitizing Agents
Cisplatin
Therapeutic Uses
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2009