Randomized Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy - Full Text View

Purpose

The doctors are testing a Wilms Tumor-1 (WT1) vaccine to see if it delays or prevents the mesothelioma from growing back after surgery. WT1 is a protein in cancer cells that regulates gene expression and causes cell growth. Mesothelioma tumors generally have high levels of WT1. The patient will be assigned to one of two treatment groups. One group will receive non-specific immunotherapy with medications called Montanide and Sargramostim (Granulocyte Macrophage Colony Stimulating Factor, GM-CSF). The other group will receive more specific immunotherapy with the WT1 vaccine plus Montanide and GM-CSF. Both Montanide and GM-CSF are commonly given along with vaccines because they have a general effect in boosting the immune response. Some researchers believe that this general increase in the immune system may have some effect in treating cancer. Some studies using GM-CSF with melanoma vaccines have suggested that it could lessen the effects of the vaccine. The addition of the WT1 proteins makes this therapy more directed to mesothelioma. The combination of WT1 vaccine with Montanide and GM-CSF has been tested in a prior trial including 9 patients with advanced mesothelioma. In that trial, the vaccine was safe and caused an immune response. The patient will have a 50% chance of being in each group. Neither the patient nor the doctor will be aware of which group they are in.

Condition	Intervention	Phase
Malignant Pleural Mesothelioma	Biological: WT-1-vaccine Montanide + GM-CSF Biological: Montanide adjuvant + GM-CSF	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Randomized Phase II Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Mesothelioma Wilms' Tumor

Drug Information available for: Sargramostim

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To assess the 1-year progression free survival in patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]
treated with WT-1 analog peptide vaccine + GM-CSF or Montanide + GM-CSF after completion of combined modality therapy for Malignant Pleural Mesothelioma (MPM). Progression free survival will be calculated from date of randomization to date of progression, death or last follow-up.

Secondary Outcome Measures:

To confirm the immunogenicity of the WT-1 analog peptide vaccine [ Time Frame: 1 year ] [ Designated as safety issue: No ]
in patients with MPM after completion of combined modality therapy.
To assess the utility of using the serum marker [ Time Frame: 1 year ] [ Designated as safety issue: No ]
(soluble mesothelin related protein (SMRP) in monitoring patients with MPM for disease progression.
overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
of patients treated with WT-1 analog peptide vaccine + GM-CSF or Montanide + GM-CSF after completion of combined modality therapy for MPM.

Estimated Enrollment:	78
Study Start Date:	December 2010
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: WT-1-vaccine Montanide + GM-CSF The study will be a randomized phase II trial to determine the 1-year progression free survival after treatment with WT-1 analog peptide vaccine in patients with MPM after completion of combined modality therapy.	Biological: WT-1-vaccine Montanide + GM-CSF Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self administered) subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.
Active Comparator: Montanide adjuvant + GM-CSF The study will be a randomized phase II trial to determine the 1-year progression free survival after treatment with WT-1 analog peptide vaccine in patients with MPM after completion of combined modality therapy.	Biological: Montanide adjuvant + GM-CSF Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self-administered)subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.

Arms

Assigned Interventions

Experimental: WT-1-vaccine Montanide + GM-CSF

The study will be a randomized phase II trial to determine the 1-year progression free survival after treatment with WT-1 analog peptide vaccine in patients with MPM after completion of combined modality therapy.

Biological: WT-1-vaccine Montanide + GM-CSF

Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self administered) subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.

Active Comparator: Montanide adjuvant + GM-CSF

The study will be a randomized phase II trial to determine the 1-year progression free survival after treatment with WT-1 analog peptide vaccine in patients with MPM after completion of combined modality therapy.

Biological: Montanide adjuvant + GM-CSF

Patients will receive 6 injections over 12 weeks. Treatment will be administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of each vaccination. Patients may self administer the Sargramostim (GM-CSF) on day -2 if they have been appropriately instructed on SQ injection administration. Patients will be informed of the expected reactions such as irritation at the injection site. Patients will keep a logbook noting the time and placement of the injection. Patients will also receive 1.0 ml of emulsion with Montanide alone or with WT-1 peptides plus Montanide. It will be administered by a nurse (it may not be self-administered)subcutaneously to the same anatomical site as the GM-CSF. This site will be marked by the patient or treating healthcare professional by a permanent marker pen.

Eligibility

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

Criteria

Inclusion Criteria:

Pathologic diagnosis of malignant pleural mesothelioma (MPM) confirmed at participating institution.
Positive immunohistochemical staining for WT-1 (greater than 10% of cells).
Completion of multimodality therapy. This must include surgical resection by either pleurectomy/decortication or extrapleural pneumonectomy. The surgery should be performed with the intent of complete resection, though patients with an R1 resection will still be eligible. Patients should have also received treatment with chemotherapy and/or radiation. Patients with an R2 resection are also eligible as long as the site of residual disease is treated post-operatively with radiotherapy.
4-12 weeks since completion of combined modality therapy.
Age > or = to 18 years
Karnofsky performance status > or = to 70%
Hematologic parameters: Absolute neutrophil count > or = to 1000/mcL, Platelets > or = to 50K/mcL.
Biochemical parameters: Total bilirubin < or = to 2.0 mg/dl, AST and ALT < or = to 2.5 x upper limits of normal, Creatinine < or = to 2.0 mg/dl.

Exclusion Criteria:

Pregnant or lactating women.
Patients with active infection requiring systemic antibiotics, antiviral, or antifungal treatments.
Patients with a serious unstable medical illness or another active cancer.
Patients taking systemic corticosteroids.
Patients with an immunodeficiency syndrome.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265433

Contacts

Contact: Lee Krug, MD	646-888-4201
Contact: Valeria Rusch, MD	212-639-5873

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Lee Krug, MD 646-888-4201
Contact: Valerie Rusch, MD 212-639-5873
Principal Investigator: Lee Krug, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Department of Defense

Investigators

Principal Investigator:

Lee Krug, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01265433 History of Changes
Other Study ID Numbers:	10-134
Study First Received:	December 21, 2010
Last Updated:	April 16, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

GM-CSF
MONTANIDE ISA 51
WT1 PEPTIDE SPECIFIC T CELLS
Vaccine
10-134

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

Neoplasms, Mesothelial
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013