A Phase II Study of Temozolomide and Survivin Long Peptide Vaccine (SurVaxM) in Patients With Progressing Metastatic Neuroendocrine Carcinomas (NECs)
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES:
- To determine the clinical efficacy (progression free survival [PFS]) of combining temozolomide and SVN53-67/M57-KLH peptide vaccine (SurVaxM) in patients with progressing NECs.
- To evaluate the safety and toxicity of the study drug combination (temozolomide + SurVaxM) in patients with progressing NECs.
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.
II. To assess anti-survivin IgG titer response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Patients who have received temozolomide in the advanced disease setting either alone or as part of a combination therapy will be excluded if they progressed while on it
- •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 may be included if there are adequately controlled viral titers and no drug-drug interactions, testing not required
研究组 & 干预措施
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: Incomplete Freund''s Adjuvant (Biological)
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: Magnetic Resonance Imaging (Procedure)
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: SVN53-67/M57-KLH Peptide Vaccine (Biological)
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: Sargramostim (Biological)
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: Computed Tomography (Procedure)
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: Biospecimen Collection (Procedure)
(temozolomide, SurVaxM)
Patients receive temozolomide PO 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 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.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: At 6 months
Summarized using frequencies and relative frequencies.
Incidence of adverse events
时间窗: Up to 1 year
Defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) version (v) 5.0. Adverse events will be summarized by attribution and grade using frequencies and relative frequencies.
次要结局
- Response(At 3, 6, 9 and 12 months from study entry)
- Titer response(Up to 1 year)
- Overall survival (OS)(At the time from treatment initiation until death due to any cause up to 1 year)
- Time to progression (TTP)(At the time from treatment initiation until disease progression, death or last follow up up to 1 year)