2024-10-15
2027-10-15
2028-10-15
132
NCT06202066
Roswell Park Cancer Institute
Roswell Park Cancer Institute
INTERVENTIONAL
Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) for the Treatment of Patients With Progressing Metastatic Neuroendocrine Tumors
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.
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.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates | Results Reporting Dates | Study Record Updates |
---|---|---|
2023-12-29 | N/A | 2024-08-01 |
2023-12-29 | N/A | 2024-08-02 |
2024-01-11 | N/A | 2024-08 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Randomized
Interventional Model:
Sequential
Masking:
Quadruple
Arms and Interventions
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: ARM I (temozolomide) 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. | PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
PROCEDURE: Magnetic Resonance Imaging
DRUG: Temozolomide
|
EXPERIMENTAL: ARM II (temozolomide, SurVaxM) 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 S | PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
BIOLOGICAL: Incomplete Freund''s Adjuvant
PROCEDURE: Magnetic Resonance Imaging
BIOLOGICAL: Sargramostim
BIOLOGICAL: SVN53-67/M57-KLH Peptide Vaccine
DRUG: Temozolomide
|
EXPERIMENTAL: PART 1 (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 Su | PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
BIOLOGICAL: Incomplete Freund''s Adjuvant
PROCEDURE: Magnetic Resonance Imaging
BIOLOGICAL: Sargramostim
BIOLOGICAL: SVN53-67/M57-KLH Peptide Vaccine
DRUG: Temozolomide
|
Primary Outcome Measures | Measure Description | Time Frame |
---|---|---|
Progression free survival (PFS) (Part 1) | Summarized using frequencies and relative frequencies. | At 6 months |
Incidence of adverse events (Part 1) | Defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) version (v) 5.0. Adverse events will be summarized by attribution and grade using frequencies and relative frequencies. | Up to 1 year |
PFS (Part 2) | Clinical benefit compared between treatment arms. PFS will be summarized by study arm using frequencies and relative frequencies. | At 6 months |
Secondary Outcome Measures | Measure Description | Time Frame |
---|---|---|
Response (Part 1) | Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Response will be summarized by time-point using frequencies and relative frequencies. Clinical benefit (best response of complete response [CR], partial response [PR] or stable disease [SD]) will be estimated and summarized using frequencies and relative frequencies, with a 95% confidence interval obtained for the clinical benefit rate. | At 3, 6, 9 and 12 months from study entry |
Overall survival (OS) (Part 1) | OS will be summarized using standard Kaplan-Meier methods, where the median will be estimated with a 95% confidence interval. | At the time from treatment initiation until death due to any cause up to 1 year |
Time to progression (TTP) (Part 1) | Defined using RECIST v1.1. TTP will be summarized using standard Kaplan-Meier methods, where the median will be estimated with a 95% confidence interval. | At the time from treatment initiation until disease progression, death or last follow up up to 1 year |
Titer response (Part 1) | Defined as anti-survivin IgG titers > 30,000 and will be summarized using frequencies and relative frequencies. | Up to 1 year |
Response (Part 2) | Assessed using RECIST v1.1. Response will be summarized by study arm and timepoint using frequencies and relative frequencies. Clinical benefit (best response of CR, PR, or SD) will be estimated and summarized by study arm using frequencies and relative frequencies, with a 95% confidence interval obtained for the clinical benefit rate. | At 6, 9, and 12 months from study entry |
OS (Part 2) | OS will be summarized by study arm using standard Kaplan-Meier methods, where the median will be estimated with a 95% confidence interval. | At time from treatment initiation until death due to any cause up to 1 year |
TTP (Part 2) | Assessed using RECIST v1.1. TTP will be summarized by study arm using standard Kaplan-Meier methods, where the median will be estimated with a 95% confidence interval. | At time from treatment initiation until disease progression, death or last follow-up up to 1 year |
Titer response (Part 2) | Defined as anti-survivin IgG titers > 30,000 and will be summarized by study arm using frequencies and relative frequencies. | Up to 1 year |
Incidence of adverse events (Part 2) | Adverse events are defined using NCI CTCAE v5.0 and will be summarized by attribution, study arm, and grade using frequencies and relative frequencies. | Up to 1 year |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
NPCF was founded on May 29, 2009 and is a 501(c)(3) organization. All donations are tax deductible.
The information and services provided by the National Pancreatic Cancer Foundation are for informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnosis or treatment. The National Pancreatic Cancer Foundation does not recommend nor endorse any specific physicians, products or treatments even though they may be mentioned on this site.
Copyright © 2024 – National Pancreatic Cancer Foundation | All Rights Reserved