Clinical Trials /

Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

NCT03879694

Description:

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.

Related Conditions:
  • Gastrointestinal Neuroendocrine Tumors
  • Lung Neuroendocrine Neoplasm
  • Pancreatic Neuroendocrine Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors
  • Official Title: A Phase I Study of Safety and Immunogenicity of Survivin Long Peptide Vaccine (SurVaxM) in Patients With Metastatic Neuroendocrine Tumors (NETs)

Clinical Trial IDs

  • ORG STUDY ID: I 79518
  • SECONDARY ID: NCI-2019-00827
  • SECONDARY ID: I 79518
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03879694

Conditions

  • Lung Atypical Carcinoid Tumor
  • Lung Typical Carcinoid Tumor
  • Metastatic Digestive System Neuroendocrine Neoplasm
  • Metastatic Lung Neuroendocrine Neoplasm
  • Metastatic Pancreatic Neuroendocrine Tumor
  • Survivin Positive

Interventions

DrugSynonymsArms
Incomplete Freund's AdjuvantFreund's Incomplete Adjuvant, IFA, ISA-51, Montanide ISA 51, Montanide ISA-51Treatment (SVN53-67/M57-KLH peptide vaccine, octreotide)
Octreotide AcetateD-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 ACTreatment (SVN53-67/M57-KLH peptide vaccine, octreotide)
Sargramostim23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, SargramostatinTreatment (SVN53-67/M57-KLH peptide vaccine, octreotide)
SVN53-67/M57-KLH Peptide VaccineTreatment (SVN53-67/M57-KLH peptide vaccine, octreotide)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (SVN53-67/M57-KLH peptide vaccine, octreotide)ExperimentalPatients 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.
  • Incomplete Freund's Adjuvant
  • Octreotide Acetate
  • Sargramostim
  • SVN53-67/M57-KLH Peptide Vaccine

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Immunogenicity of SVN53-67/M57-KLH peptide vaccine
Time Frame:Baseline up to 15 months
Safety Issue:
Description: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.
Measure:Immunogenicity of SVN53-67/M57-KLH peptide vaccine
Time Frame:Baseline up to 15 months
Safety Issue:
Description: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.
Measure:Rate of progression
Time Frame:Up to 15 months
Safety Issue:
Description: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.
Measure:Clinical benefit
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Time to progression (TTP)
Time Frame:From enrollment to first documented progression per RECISTv1.1, assessed up to 15 months
Safety Issue:
Description: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.
Measure:Overall response rate (ORR)
Time Frame:Up to 15 months
Safety Issue:
Description:Measured by RECIST v1.1.
Measure:Duration of response (DOR)
Time Frame:Up to 15 months
Safety Issue:
Description:Measured by RECIST v1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Roswell Park Cancer Institute

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