WT-1 Analog Peptide Vaccine in Malignant Pleural Mesothelioma After Combined Modality Therapy

Study Overview
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Brief Summary
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Study of 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.

Detailed Description
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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.This study was originally designed to have two treatment groups. One group received non-specific immunotherapy with medications called Montanide and Sargramostim (Granulocyte Macrophage Colony Stimulating Factor, GM-CSF). Enrollment to this group has stopped The other group, which continues receives 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.

Official Title
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Randomized Phase II Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy

Conditions
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Malignant Pleural Mesothelioma

Intervention / Treatment
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* Biological: WT-1-vaccine Montanide + GM-CSF
* Biological: Montanide adjuvant + GM-CSF (This arm is closed)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WT-1-vaccine Montanide + GM-CSF<br>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<br>* 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.<br>|
| Active Comparator: Montanide adjuvant + GM-CSF (This arm is closed)<br>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 (This arm is closed)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the 1-year progression free survival in patients | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To confirm the immunogenicity of the WT-1 analog peptide vaccine | in patients with MPM after completion of combined modality therapy. | 1 year | 
| To assess the utility of using the serum marker | (soluble mesothelin related protein (SMRP) in monitoring patients with MPM for disease progression. | 1 year | 
| overall survival | of patients treated with WT-1 analog peptide vaccine + GM-CSF or Montanide + GM-CSF after completion of combined modality therapy for MPM. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GM-CSF, MONTANIDE ISA 51, WT1 PEPTIDE SPECIFIC T CELLS, Vaccine, 10-134