Survivin Long Peptide Vaccine in Treating Patients With Metastatic Neuroendocrine Tumors

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.

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.