A Phase Ib Trial of Neoadjuvant PalloV-CC (Particle-delivered, Allogeneic Tumor Cell Lysate Vaccine for Colon Cancer) in Colon Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Primary Safety Endpoint-Overall number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
研究概览
简要总结
This study is a phase Ib prospective, open label study evaluating the effect of vaccination on the immune microenvironment of cancers with results compared to banked tissue from historical controls. Prospectively vaccinated patients will also serve as their own controls by comparing the immune microenvironment of the tumor in pre-treatment biopsies to post-treatment surgical specimens. This is also a dose-escalation study with consecutive enrollment and advancement of cohorts in an overlapping fashion.
详细描述
This is a single arm, open label, phase Ib trial of neoadjuvant vaccination in colon cancer. The primary endpoint is the safety and toxicity of the vaccine. The primary immunologic endpoint is the impact of vaccination on the tumor microenvironment compared to prospectively evaluated, tissue banked specimens from historical controls. The tumor microenvironment will also be compared in matched pre- and post-treatment tissue samples in vaccinated subjects. Patients with endoscopic biopsy proven colon cancer will be identified by the staff in the gastroenterology, surgery, and/or the hematology/oncology clinics at the individual study sites. A research nurse, study coordinator, or study investigator will approach these patients about being in the trial and will introduce the trial to the prospective volunteer patient. If the patient is interested and appears eligible, the nurse, study coordinator, or investigator will arrange an appointment to counsel and consent the patient. Once consent is obtained, the nurse, study coordinator, or investigator will thoroughly screen the patient for inclusion and exclusion eligibility criteria.
If volunteers meet all inclusion criteria and none of the exclusion criteria and agree to participate, they will continue in the study, consented and enrolled for treatment assignment. Enrollment will start in cohort 1 with enrollment of 6 patients, and follow sequentially into the remaining cohorts, until all cohorts are completed. After treatment of all 6 patients in each dose cohort, a comprehensive safety analysis will be performed for short-term toxicity. If no dose limiting toxicity (DLT, >grade 2, related, or serious adverse event (SAE)) is found, then the next cohort will be enrolled. If three patients in a given dose cohort experience a DLT, then that dose will be determined to be the maximal tolerated dose (MTD), and the next dose cohort will not be initiated. At the completion of dosing of cohorts (last surgical colectomy performed), a comprehensive safety analysis will be performed for long-term toxicity. If the MTD is not reached, then a total of 24 patients will be enrolled.
Treatment cohorts (each n=6, total of n=24):
- 1 x 10^8 particles of PalloV-CC
- 2 x 10^8 particles of PalloV-CC
- 4 x 10^8 particles of PalloV-CC
- 8 x 10^8 particles of PalloV-CC
PalloV-CC is inoculated weekly via intradermal injection. There will be sequential enrollment of dose-escalation cohorts (Appendix A), each patient treatment period is 4 weeks (Appendix B). Patients will conclude treatment with colectomy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Stage I-IV (resectable) colon cancer patients identified prior to their definitive surgery
- •Diagnosis definitively confirmed by endoscopic biopsy with tumor tissue slides available for analysis
- •Asymptomatic and capable of waiting 4 weeks prior to definitive surgery
- •ECOG 0-1 performance
- •Not involved in other clinical trials
- •Capable of giving informed consent
排除标准
- •Symptoms of obstruction or GI bleeding that necessitate more urgent surgical intervention
- •Cancer not definitively confirmed on endoscopic biopsy (i.e., Only high-grade dysplasia or adenoma identified, even if malignancy is suspected)
- •Known immune deficiency disease or HIV, active HBV, or active HCV
- •Steroids or other immunosuppressants received within 6 weeks of enrollment
- •Any colon cancer directed treatment (chemotherapy or radiation) received or planned prior to surgical resection
- •A history of any hematologic malignancy or myeloproliferative disease within 5 years prior to enrollment
- •Leukopenia or neutropenia within two weeks of presentation
- •ECOG >/= 2
- •Pregnancy (serum or urine HCG) or breast feeding
- •Tbili >1.8, Cr >2, Hgb <10, platelet count <50,000, WBC <2,000
结局指标
主要结局
Primary Safety Endpoint-Overall number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
时间窗: 1 year for all 4 cohorts to enroll and undergo treatment.
To determine the overall safety and toxicity of the PalloV CC vaccine by analyzing number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Primary Safety Endpoint-Per Dosing Cohort number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
时间窗: 1 year for all 4 cohorts to enroll and undergo treatment.
To determine the safety and toxicity of the PalloV CC vaccine per dosing cohorts by analyzing number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Primary Immunologic Endpoint-Overall Immunoscore of the tumor microenvironment
时间窗: 1 year for all 4 cohorts to enroll and undergo treatment.
To determine the effect of vaccination on the tumor microenvironment in colon cancer by comparing the proportion of subjects with high Immunoscore (scale range: low, intermediate, high) in all vaccinated subjects to historical control subjects.
Primary Immunologic Endpoint-Per Dosing Cohort Immunoscore of the tumor microenvironment
时间窗: 1 year for all 4 cohorts to enroll and undergo treatment.
To determine the effect of vaccination on the tumor microenvironment in colon cancer by comparing the proportion of subjects Immunoscore (scale range: low, intermediate, high) in vaccinated subjects per dosing cohorts to historical control subjects Immunoscore (scale range: low, intermediate, high).
次要结局
- Secondary Endpoint-CD4+ and regulatory T cells expression comparison within the Tumor Microenvironment(1 year for all 4 cohorts to enroll and undergo treatment.)
- Secondary Endpoint-Effect Tumor Microenvironment measured via Immunoscore(1 year for all 4 cohorts to enroll and undergo treatment.)
- Secondary Endpoint-Immunologic comparison of evaluations of tumor microenvironment(1 year for all 4 cohorts to enroll and undergo treatment.)
- Secondary Endpoint-PD-L1 expression comparison within the Tumor Microenvironment(1 year for all 4 cohorts to enroll and undergo treatment.)
研究者
George E. Peoples
CEO, Cancer Insight, LLC
Cancer Insight, LLC