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

Malignant Pleural Mesothelioma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01265433
• Other study ID #: 10-134
• Status: Completed
• Phase: Phase 2
• Start date: December 21, 2010
• Est. completion date: July 25, 2017

Study information

• Verified date: November 2018
• Source: Sellas Life Sciences Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: July 25, 2017
• Est. primary completion date: July 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

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.
• Montanide adjuvant + GM-CSF (This arm is closed)
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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Sellas Life Sciences Group	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To confirm the immunogenicity of the WT-1 analog peptide vaccine	in patients with MPM after completion of combined modality therapy.	1 year
Secondary	To assess the utility of using the serum marker	(soluble mesothelin related protein (SMRP) in monitoring patients with MPM for disease progression.	1 year
Secondary	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

External Links

•   Memorial Sloan Kettering Cancer Center