Trial Title:
Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) for the Treatment of Patients With Progressing Metastatic Neuroendocrine Tumors
NCT ID:
NCT06202066
Condition:
Digestive System Neuroendocrine Neoplasm
Lung Neuroendocrine Neoplasm
Malignant Solid Neoplasm
Pancreatic Neuroendocrine Neoplasm
Conditions: Official terms:
Neoplasms
Neuroendocrine Tumors
Temozolomide
Sargramostim
Monatide (IMS 3015)
Freund's Adjuvant
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
This is a two-part study. Part 1 is an open-label, single arm study. Part 2 is a blinded,
randomized two-arm study. Part 2 will only proceed if part 1 is successful.
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
All subjects will be unblinded to the research team at the time of the final analysis. In
the presence of unexpected or severe adverse events, subjects may be unblinded to the
Data Safety and Monitoring Committee upon request.
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
ARM I (temozolomide)
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
ARM I (temozolomide)
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Incomplete Freund''s Adjuvant
Description:
Given SC
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
Freund's Incomplete Adjuvant
Other name:
IFA
Other name:
incomplete Freund's adjuvant
Other name:
ISA-51
Other name:
Montanide ISA 51
Other name:
Montanide ISA-51
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
ARM I (temozolomide)
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Sargramostim
Description:
Given SC
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
23-L-Leucinecolony-Stimulating Factor 2
Other name:
DRG-0012
Other name:
Leukine
Other name:
Prokine
Other name:
rhu GM-CFS
Other name:
Sagramostim
Other name:
Sargramostatin
Intervention type:
Biological
Intervention name:
SVN53-67/M57-KLH Peptide Vaccine
Description:
Given SC
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
SurVaxM
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Given PO
Arm group label:
ARM I (temozolomide)
Arm group label:
ARM II (temozolomide, SurVaxM)
Arm group label:
PART 1 (temozolomide, SurVaxM)
Other name:
CCRG-81045
Other name:
Gliotem
Other name:
Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
Other name:
M & B 39831
Other name:
M and B 39831
Other name:
Methazolastone
Other name:
RP-46161
Other name:
SCH 52365
Other name:
Temcad
Other name:
Temizole
Other name:
Temodal
Other name:
Temodar
Other name:
Temomedac
Other name:
TMZ
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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
- Patients must have documented radiographic progression, determined as clinically
significant by the treating provider, within the last twelve months on 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 (e.g. lanreotide,
octreotide, everolimus, sunitinib, or lutetium Lu 177 dotatate)
- 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
- 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 or HIV may be included if there are
adequately controlled viral titers and no drug-drug interactions
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Contact:
Last name:
Renuka V. Iyer
Phone:
716-845-8195
Email:
Renuka.Iyer@RoswellPark.org
Investigator:
Last name:
Renuka V. Iyer
Email:
Principal Investigator
Start date:
December 15, 2024
Completion date:
October 15, 2028
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06202066
