Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) for the Treatment of Patients With Progressing Metastatic Neuroendocrine Tumors

Malignant Solid Neoplasm Clinical Trial

Official title: A Phase II Study of Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) in Patients With Progressing Metastatic Neuroendocrine Tumors (NETs)

Status Not yet recruiting

Clinical Trial Summary

This phase II trial compares the safety and effect of temozolomide combined with survivin long peptide vaccine (SurVaxM) to temozolomide alone in patients with neuroendocrine tumors (NET) that has spread from where it first started (primary site) to other places in the body (metastatic) and is growing, spreading or getting worse (progressing). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Survivin, a protein, is expressed in 50% of patients that have neuroendocrine tumors and, is associated with poor outcomes. SVN53-67/M57-KLH peptide vaccine (SurVaxM) is a vaccine that has been shown to produce an immune system response against cancer cells that express a survivin and may block the growth of new tumor cells. Giving temozolomide with SurVaxM may kill more tumor cells in patients with progressing metastatic neuroendocrine tumors.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the clinical efficacy (progression free survival [PFS]) of combining temozolomide and SVN53-67/M57-KLH peptide vaccine (SurVaxM) in patients with progressing NETs. (Part 1: Phase IIa Study) II. To evaluate the safety and toxicity of the study drug combination (temozolomide + SurVaxM) in patients with progressing NETs. (Part 1: Phase IIa Study) III. To evaluate the clinical efficacy (PFS) between patients treated with temozolomide alone compared to patients treated with the combination of SurVaxM + temozolomide. (Part 2: Phase IIb Study)

SECONDARY OBJECTIVES:

I. To assess clinical benefit (including complete response, partial response and stable disease as defined by Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) at 3 months, 6 months, 9 months, and 12 months from study entry. (Part 1: Phase IIa Study) II. To assess anti-survivin IgG titer response. (Part 1: Phase IIa Study) III. Compare clinical benefit. (Part 2: Phase IIb Study) IV. Assess anti-survivin IgG titer response. (Part 2: Phase IIb Study) V. Assess safety. (Part 2: Phase IIb Study)

EXPLORATORY OBJECTIVES:

I. To explore immune markers associated with clinical responses to SurVaxM in peripheral blood of NETs patients. (Part 2: Phase IIb Study) II. To assess the methylguanine methyltransferase (MGMT) status of all patients and correlate with response. (Part 2: Phase IIb Study) III. To assess the tumor growth rate (TGR) on radiographic imaging prior to study enrollment and while on study. (Part 2: Phase IIb Study)

OUTLINE: Patients are assigned to 1 of 2 parts.

PART 1: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity and can be continued at investigators discretion at end of treatment. Patients also receive SurVaxM with incomplete Freund's adjuvant (montanide ISA-51) subcutaneously (SC) and sargramostim SC once every 2 weeks for 4 doses. Patients with clinical benefit after 4 doses of SurVaxM and remain free of tumor progression and unacceptable toxicity may receive 3 additional doses on weeks 24, 36, and 48. Additionally, patients undergo blood sample collection, computed tomography (CT) scans or magnetic resonance imaging (MRI) scans throughout study.

PART 2: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT scans or MRI scans throughout study.

ARM II: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity and can be continued at investigators discretion at end of treatment. Patients also receive SurVaxM with montanide ISA-51 SC and sargramostim SC once every 2 weeks for 4 doses. Patients with clinical benefit after 4 doses of SurVaxM and remain free of tumor progression and unacceptable toxicity may receive 3 additional doses on weeks 24, 36, and 48. Additionally, patients undergo blood sample collection, CT scans or MRI scans throughout study.

After completion of study treatment, patients are followed up at 30 days. ;

Related Conditions & MeSH terms

• Digestive System Neuroendocrine Neoplasm
• Lung Neuroendocrine Neoplasm
• Malignant Solid Neoplasm
• Neoplasms
• Neuroendocrine Tumors

• NCT number: NCT06202066
• Study type: Interventional
• Source: Roswell Park Cancer Institute
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 15, 2024
• Completion date: January 15, 2028