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

NCT ID: NCT06202066

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-15

Study Completion Date

2028-10-15

Brief Summary

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This phase IIa 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.

Detailed Description

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PRIMARY OBJECTIVES:

* To determine the clinical efficacy (progression free survival \[PFS\]) of combining temozolomide and SVN53-67/M57-KLH peptide vaccine (SurVaxM) in patients with progressing NECs.
* To evaluate the safety and toxicity of the study drug combination (temozolomide + SurVaxM) in patients with progressing NECs.

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.

II. To assess anti-survivin IgG titer response.

EXPLORATORY OBJECTIVES:

I. To explore immune markers associated with clinical responses to SurVaxM in peripheral blood of NETs patients.

II. To assess the methylguanine methyltransferase (MGMT) status of all patients and correlate with response.

III. To assess the tumor growth rate (TGR) on radiographic imaging prior to study enrollment and while on study.

OUTLINE:

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.

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

Conditions

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Digestive System Neuroendocrine Neoplasm Lung Neuroendocrine Neoplasm Malignant Solid Neoplasm Pancreatic Neuroendocrine Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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(temozolomide, SurVaxM)

Patients receive temozolomide PO 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 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Incomplete Freund''s Adjuvant

Intervention Type BIOLOGICAL

Given SC

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Sargramostim

Intervention Type BIOLOGICAL

Given SC

SVN53-67/M57-KLH Peptide Vaccine

Intervention Type BIOLOGICAL

Given SC

Temozolomide

Intervention Type DRUG

Given PO

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Incomplete Freund''s Adjuvant

Given SC

Intervention Type BIOLOGICAL

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Sargramostim

Given SC

Intervention Type BIOLOGICAL

SVN53-67/M57-KLH Peptide Vaccine

Given SC

Intervention Type BIOLOGICAL

Temozolomide

Given PO

Intervention Type DRUG

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography Freund's Incomplete Adjuvant IFA incomplete Freund's adjuvant ISA-51 Montanide ISA 51 Montanide ISA-51 Magnetic Resonance Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin SurVaxM CCRG-81045 Gliotem Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temizole Temodal Temodar Temomedac TMZ

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years of age
* Have a Karnofsky performance status ≥ 80 or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (i.e. the patient must be able to care for himself/ herself with occasional help from others)
* Measurable, pathologically confirmed diagnosis of neuroendocrine tumor of gastrointestinal, pancreatic, or lung origin with ki67\>20% or neuroendocrine carcinoma of any origin excluding small cell lung carcinoma (well-differentiated G3 NETs and extrapulmonary NECs).
* Patients must have documented radiographic progression, determined as clinically significant by the treating provider, within the last twelve months on two CT or MRI scans performed at least four weeks apart per RECIST v1.1 criteria. In the case of retreatment, progression may be defined by the treating provider (e.g., clinical, radiographic, biochemical)
* Patients must have failed at least one prior systemic therapy
* Patients who have been on somatostatin analogues (SSA) may continue to take SSA while on study treatment
* Archival neuroendocrine tumor tissue must test positive for survivin presence by clinical immunohistochemistry prior to study enrollment
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (obtained within 14 days prior to enrollment)
* Platelets ≥ 100 x 10\^9/L (obtained within 14 days prior to enrollment)
* Hemoglobin (Hgb) \> 9g/dL (obtained within 14 days prior to enrollment)
* Plasma total bilirubin: ≤ 1.5 x upper limit of normal (ULN) (obtained within 14 days prior to enrollment)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 4 x ULN (obtained within 14 days prior to enrollment)
* Creatinine clearance ≥ 60 mL/min (per Cockroft-Gault equation) (obtained within 14 days prior to enrollment)
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet the following criteria:

* No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices, which carries a significant risk of bleeding in investigator's opinion)
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

* Patients who have received temozolomide in the advanced disease setting either alone or as part of a combination therapy will be excluded if they progressed while on it
* Has received prior treatment with SurVaxM
* Received an investigational agent within 30 days prior to enrollment
* Participants who have received checkpoint inhibitors within 3 months prior to study enrollment or, those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, bradycardia, tachycardia or psychiatric illness/social situations that would limit compliance with study requirements and, which in the treating physicians' opinion would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
* Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study
* Known history of an autoimmune disorder
* Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness
* Systemic corticosteroid therapy \> 2mg of dexamethasone or equivalent per day at study entry
* Pregnant or nursing female participants
* Unwilling or unable to follow protocol requirements
* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
* Patients with Hepatitis B or Hepatitis C may be included if there are adequately controlled viral titers and no drug-drug interactions, testing not required
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Renuka V Iyer

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

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Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2023-09345

Identifier Type: REGISTRY

Identifier Source: secondary_id

I 3622923

Identifier Type: OTHER

Identifier Source: secondary_id

I 3622923

Identifier Type: -

Identifier Source: org_study_id