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Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03879694
Recruitment Status : Recruiting
First Posted : March 19, 2019
Last Update Posted : August 6, 2020
Sponsor:
Collaborators:
NeuroEndocrine Tumor Research Foundation (NETRF)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE March 13, 2019
First Posted Date  ICMJE March 19, 2019
Last Update Posted Date August 6, 2020
Actual Study Start Date  ICMJE June 13, 2019
Estimated Primary Completion Date December 17, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
Incidence of adverse events of SVN53-67/M57-KLH peptide vaccine in combination with octreotide acetate in patients with neuroendocrine tumors [ Time Frame: Up to 15 months ]
Will be assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will consider a toxicity to be an adverse event that is possibly, probably or definitely related to treatment. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. Will be quantified using the observed rates of the adverse events, serious adverse events (SAE) and regimen limiting toxicities. Toxicity rates will be described using upper 1-sided 95% Jeffreys binomial confidence intervals.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
  • Immunogenicity of SVN53-67/M57-KLH peptide vaccine [ Time Frame: Baseline up to 15 months ]
    Survivin-specific CD8+ responses will be measured individually at baseline, 12 weeks and end of-study. These measures will be summarized by descriptive statistics (means, medians, quartiles, etc.). Confidence intervals will be constructed for the median and the mean. Exploratory graphical analysis will be used to discover associations among variables.
  • Immunogenicity of SVN53-67/M57-KLH peptide vaccine [ Time Frame: Baseline up to 15 months ]
    Anti-survivin antibody (humoral) responses will be measured individually at baseline, 12 weeks and end of-study. These measures will be summarized by descriptive statistics (means, medians, quartiles, etc.). Confidence intervals will be constructed for the median and the mean. Exploratory graphical analysis will be used to discover associations among variables.
  • Rate of progression [ Time Frame: Up to 15 months ]
    Will be based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 on computed tomography scan and comparison rate prior to start of treatment.
  • Clinical benefit [ Time Frame: Up to 12 months ]
    Will be assessed with RECIST v1.1. Clinical Benefit (CB) is defined as number of patients having best overall response as complete response (CR), partial response (PR) or stable disease (SD). The estimated distribution of CB will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
  • Time to progression (TTP) [ Time Frame: From enrollment to first documented progression per RECISTv1.1, assessed up to 15 months ]
    The TTP of each patient will be compared to TTP prior to study entry. The analysis will be descriptive and reported separately for each patient.
  • Overall response rate (ORR) [ Time Frame: Up to 15 months ]
    Measured by RECIST v1.1.
  • Duration of response (DOR) [ Time Frame: Up to 15 months ]
    Measured by RECIST v1.1.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 14, 2019)
  • Serum levels of chromogranin A, serotonin and 5-HIAA [ Time Frame: Baseline up to 15 months ]
    Exploratory graphical analysis will be used to discover associations among variables.
  • Serum levels of serotonin and 5-HIAA [ Time Frame: Baseline up to 15 months ]
    Exploratory graphical analysis will be used to discover associations among variables
  • Serum levels of 5-HIAA [ Time Frame: Baseline up to 15 months ]
    Exploratory graphical analysis will be used to discover associations among variables
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors
Official Title  ICMJE A Phase I Study of Safety and Immunogenicity of Survivin Long Peptide Vaccine (SurVaxM) in Patients With Metastatic Neuroendocrine Tumors (NETs)
Brief Summary This phase I trial studies the side effects of survivin long peptide vaccine and how it works with the immune system in treating patients with neuroendocrine tumors that have spread to other parts of the body (metastatic). Tumor cells make proteins that are not usually produced by normal cells. The body sees these proteins as not belonging and sends white blood cells called T cells to attack the tumor cells that contain these proteins. By vaccinating with small pieces of these proteins called peptides, the immune system can be made to kill tumor cells. Giving survivin long peptide vaccine to patients who have survivin expression in their tumors may create an immune response in the blood that is directed against neuroendocrine tumors.
Detailed Description

PRIMARY OBJECTIVES:

I. To assess safety, tolerability and toxicity of SVN53-67/M57-KLH peptide vaccine (SurVaxM) in emulsion with incomplete Freund's adjuvant (montanide ISA 51) and given subcutaneously with sargramostim (granulocyte macrophage-colony-stimulating factor [GM-CSF]) in combination with a somatostatin analogue, octreotide acetate (Sandostatin LAR) in patients with survivin positive metastatic neuroendocrine tumors (NETs).

SECONDARY OBJECTIVES:

I. To determine 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 6 months, 9 months and 12 months from study entry.

II. To evaluate the immunogenicity of SurVaxM in NETs by measuring anti-survivin antibody levels and anti-tumor T-cell responses in peripheral blood.

III. To determine time to progression (TTP) compared to prior to study entry, in patients with metastatic NETs treated with SurVaxM and octreotide who experienced progression on therapy with a somatostatin analogue.

EXPLORATORY OBJECTIVES:

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

OUTLINE:

Patients receive a SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant subcutaneously (SC) and sargramostim SC on day 0. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Patients also receive octreotide acetate intramuscularly (IM) on day 0. Cycles of octreotide acetate repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who remain free of tumor progression at 6 months and do not develop any regimen-related toxicity or serious adverse events will be eligible to receive additional doses of the vaccine and sargramostim every 3 months, for up to 1 year from the start of treatment.

After completion of study treatment, patients are followed up for 3 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lung Atypical Carcinoid Tumor
  • Lung Typical Carcinoid Tumor
  • Metastatic Pancreatic Neuroendocrine Tumor
Intervention  ICMJE
  • Biological: Incomplete Freund's Adjuvant
    Given SC
    Other Names:
    • Freund's Incomplete Adjuvant
    • IFA
    • ISA-51
    • Montanide ISA 51
    • Montanide ISA-51
  • Drug: Octreotide Acetate
    Given IM
    Other Names:
    • D-Phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[(1R,2R)-2-hydroxy-1-(hyroxymethyl)propyl]-L-cysteinamide, Cyclic (2->7)-disulfide, Acetate (Salt)
    • Longastatin
    • Longastatina
    • Samilstin
    • Sandostatin
    • Sandostatin Lar Depot
    • Sandostatina
    • Sandostatine
    • SMS 201-995
    • SMS 201-995 AC
  • Biological: Sargramostim
    Given SC
    Other Names:
    • 23-L-Leucinecolony-Stimulating Factor 2
    • DRG-0012
    • Leukine
    • Prokine
    • rhu GM-CFS
    • Sagramostim
    • Sargramostatin
  • Biological: SVN53-67/M57-KLH Peptide Vaccine
    Given SC
Study Arms  ICMJE Experimental: Treatment (SVN53-67/M57-KLH peptide vaccine, octreotide)
Patients receive a SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC on day 0. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Patients also receive octreotide acetate IM on day 0. Cycles of octreotide acetate repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who remain free of tumor progression at 6 months and do not develop any regimen-related toxicity or serious adverse events will be eligible to receive additional doses of the vaccine and sargramostim every 3 months, for up to 1 year from the start of treatment.
Interventions:
  • Biological: Incomplete Freund's Adjuvant
  • Drug: Octreotide Acetate
  • Biological: Sargramostim
  • Biological: SVN53-67/M57-KLH Peptide Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2019)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 17, 2020
Estimated Primary Completion Date December 17, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have a Karnofsky performance status >= 70 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).
  • Pathologically confirmed diagnosis of neuroendocrine tumor of gastrointestinal, pancreatic or lung origin.
  • Previous treatment with somatostatin analogues and documented progression within last 6 months on 2 successive computed tomography (CT) scans, at least 4 weeks apart, as defined by RECIST v1.1 while on somatostatin analogue.
  • Availability of adequate tissue from previous biopsy of neuroendocrine tumor to test for survivin expression by tumor cells using immunohistochemistry.
  • 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) > 9.0 g/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) =< 4.0 x ULN (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).
  • Creatinine =< 1.8 mg/dl (obtained within 14 days of enrollment).
  • 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 and, have a negative pregnancy test prior to starting study treatment. 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 or legal representative 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:

  • The patient must not have received any immunotherapy for any malignancy.
  • Patients with serious concurrent infection or medical illness, 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 who are pregnant or breast-feeding.
  • 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.
  • Previous local therapy (e.g. chemo-embolization, bland, or radio-embolization) is allowed if completed > 6 weeks prior to randomization. For subjects who received local therapy prior to randomization, there must be documented growth of measurable disease within the embolization field prior to study.
  • Unwilling or unable to follow protocol requirements.
  • Systemic corticosteroid therapy > 2 mg of dexamethasone or equivalent per day at study entry.
  • Any condition which in the investigator?s opinion deems the participant an unsuitable candidate to receive study drug.
  • Received an investigational agent within 30 days prior to enrollment.
  • Clinically significant cardiac arrhythmia, bradycardia, tachycardia that would compromise patient safety or the outcome of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03879694
Other Study ID Numbers  ICMJE I 79518
NCI-2019-00827 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 79518 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • NeuroEndocrine Tumor Research Foundation (NETRF)
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Renuka V Iyer Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP