A Phase I Study Combining NeoVax, a Personalized NeoAntigen Cancer Vaccine, With Ipilimumab to Treat High-risk Renal Cell Carcinoma
概览
- 阶段
- 1 期
- 干预措施
- NeoVax
- 疾病 / 适应症
- Kidney Cancer
- 发起方
- Patrick Ott, MD, PhD
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Number of participants with dose-limiting toxicity (DLT) experienced within 49 days (7 weeks) of treatment initiation as assessed by CTCAE v4.0
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
This research study is evaluating a new type of Kidney Cancer vaccine called "Personalized NeoAntigen Cancer Vaccine"as a possible treatment for Kidney Cancer.
The following intervention will be involved in this study:
- Personalized Neoantigen Vaccine
- Poly-ICLC (Hiltonol)
- Ipilimumab
详细描述
This research study is a Phase I clinical trial, which tests the safety of an investigational kidney cancer vaccine and also tries to define the appropriate dose of the investigational kidney cancer vaccine to use for further studies. "Investigational" means that the kidney cancer vaccine, in this case the Personalized Neoantigen Cancer Vaccine, is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not approved the Personalized Cancer Vaccine for any use in patients, including people with kidney cancer. Poly-ICLC (also called Hiltonol) is an experimental "viral mimic" and an activator of immunity. Poly-ICLC is an investigational drug, meaning the FDA has not approved it as a treatment for any disease. Personalized NeoAntigen Cancer Vaccine: The purpose of this study is to determine if it is possible to make and administer safely a vaccine against kidney cancer by using information gained from specific characteristics of the participant's own kidney cancer. It is known that kidney cancers have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the participant's body fight any tumor cells that could cause the kidney cancer to come back in the future. The study will examine the safety of the vaccine when given at several different time points and will examine the participant's blood cells for signs that the vaccine induced an immune response. Ipilimumab (Yervoy™) is an antibody that has been approved by the United States Food and Drug Administration (FDA) for the treatment of melanoma. In this research study, the investigators are looking at the safety and tolerability of the Personalized NeoAntigen Cancer Vaccine combined with Ipilimumab as well as the body's immune response to the vaccine. Ipilimumab will be delivered as an injection given underneath the skin rather than injected in the vein in proximity to each vaccination site in order to 1) direct anti-CTLA4 activity to the vaccine-draining lymph nodes and 2) limit potential toxic effects.
研究者
Patrick Ott, MD, PhD
MD
Dana-Farber Cancer Institute
入排标准
入选标准
- •for Initial Registration:
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients should have suspected stage III or stage IV clear cell renal cell carcinoma (ccRCC), with anticipation that all disease can be surgically resected. Confirmation of clear cell histology, final stage (III or IV), and removal of all disease will be done after the surgery, and will be required for further participation of the trial.
- •Patient is agreeable to allow tumor and normal tissue samples to be submitted for complete exome and transcription sequencing.
- •Patients undergoing a potentially curative metastatectomy are eligible if the tumor tissue from the surgery is enough to make a vaccine.
- •ECOG (Eastern Cooperative Oncology Group) performance status ≤
- •Age ≥ 18 years.
- •Participants must have normal organ and marrow function as defined below:
- •leukocytes ≥3,000/mcL (microliter)
- •absolute neutrophil count ≥1,500/mcL
排除标准
- •Prior treatment with immune-modulatory agents including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, CD40 stimulation, or CD137 stimulation.
- •Prior investigational ccRCC-directed cancer vaccine therapy.
- •Patients with active brain metastases or leptomeningeal disease.
- •Prior systemic therapy, including targeted therapy such as VEGF or mTOR inhibitors unless it is \>6 months between last dose of drug and first vaccination with NeoVax. Systemic therapy is allowed only if prior therapy was not immune therapy (i.e. VEGF TKI), and it was \>6 months ago.
- •Treatment with other investigational products within the last 2 months prior to entry into this study.
- •Previous bone marrow or stem cell transplant.
- •Concomitant therapy with any anti-cancer agents for ACTIVE cancer treatment, other investigational anti-cancer therapies, or immunosuppressive agents; chronic use of systemic corticosteroids with prednisone \>10 mg/day.
- •Use of a non-oncology vaccine therapy for prevention of infectious diseases (with the exception of vaccination against the SARS-CoV-2 virus for the prevention of COVID-19 disease) is not allowed for 4 weeks prior to day 1, until 8 weeks after last study dose. Given the severity of the COVID-19 pandemic, vaccination specifically against the SARS-CoV-2 virus for the prevention of COVID-19 is ALLOWED in this study.
- •History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases.
- •History of or current active autoimmune diseases, \[e.g. including but not limited to inflammatory bowel diseases \[IBD\], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.\].
研究组 & 干预措施
Neovax in Combination with Ipilimumab
Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22 * In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20 Ipilimumab will be injected within 1 cm of each NeoVax administration
干预措施: NeoVax
Neovax in Combination with Ipilimumab
Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22 * In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20 Ipilimumab will be injected within 1 cm of each NeoVax administration
干预措施: Ipilimumab
NeoVax alone
Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22 * In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20)
干预措施: NeoVax
结局指标
主要结局
Number of participants with dose-limiting toxicity (DLT) experienced within 49 days (7 weeks) of treatment initiation as assessed by CTCAE v4.0
时间窗: 49 days
次要结局
- Number of participants alive at 2 years(2 years)
- Number of participants with NeoVax induced IFN γ (interferon γ) T-cell Response against neoepitopes measured by ELISPOT at week 16(16 weeks)