A Phase II Study of Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) in Patients With Progressing Metastatic Neuroendocrine Carcinomas (NECs)
This phase IIa 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.
• 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 thoracic origin with ki67\>20% (well-differentiated G3 NETs) or neuroendocrine carcinoma of any origin excluding small cell lung carcinoma
• Patients must have documented radiographic progression, determined as clinically significant by the treating provider, within the last twelve months on two 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
• 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