Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
Background:
ETBX-011, ETBX-061, and ETBX-051 are cancer vaccines. Their goal is to teach the immune system to target and kill cancer cells. The vaccines target 3 proteins found in many types of cancer. Researchers think targeting all 3 proteins in unison will have the best results.
Objective:
To test the safety of combining ETBX-011, ETBX-061, and ETBX-051 and their effects on the immune system.
Eligibility:
People ages 18 and older with advanced cancer that has not responded to standard therapies
Design:
Participants will be screened with:
Medical history
Physical exam
Blood, urine, and heart tests
Scan: They will lie in a machine that takes pictures of the body.
Participants will receive the 3 vaccines through 3 shots under the skin every 3 weeks for 3 doses, then every 8 weeks for up to 1 year. They will have blood and urine tests at each vaccine visit. They will have scans and other measurements of their tumor after 9 weeks and then at their vaccine visits every 8 weeks.
Participants will keep a diary of symptoms at the injection site.
Participants will have a visit 90 days after their final treatment. This will include a physical exam and blood and urine tests. If they have any ongoing side effects, they will be followed until these end or are not changing.
After this visit, they will be called every 3 months for the first year, every 6 months for the next 2 years, then every 12 months for another 2 years to see how they are doing.
Participants will have the option to enroll in a long-term follow-up study.
...
详细描述
Background:
- The overall goal of the current project is to expand our immunotherapeutic approach for the treatment of advanced cancer employing a multi-targeted approach.
- Therapeutic cancer vaccines targeting overexpressed proteins offer a potential method to activate T cells against tumors.
- A novel adenovirus based vaccine targeting three (3) human tumor associated antigens (TAA), carcinoembryonic antigen (CEA), mucin-1 (MUC1), and brachyury, respectively has demonstrated anti-tumor cytolytic T cell responses in pre-clinical animal models of cancer.
Objectives:
-To determine the overall safety and recommended phase 2 dose of a combination of three immunotherapeutic vaccines (ETBX-011/ETBX-061/ETBX-051), when administered subcutaneously (SC) to subjects with advanced solid tumors
Eligibility:
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Age greater than or equal to 18 years (male and female).
- •Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)'s guidelines.
- •Subjects with cytologically or histologically confirmed locally advanced or metastatic solid tumor malignancy.
- •Subjects must have completed or had disease progression on at least one prior line of disease-appropriate therapy or not be candidates for therapy of proven efficacy for their disease.
- •Subjects may have measurable or non-measurable but evaluable. Subjects with surgically resected locally advanced or metastatic disease at high risk of relapse are also eligible.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- •Subjects who have received prior carcinoembryonic antigen (CEA), mucin-1 (MUC1), and/or Brachyury-targeted immunotherapy (vaccine) are eligible for this trial if this treatment was discontinued at least 4 weeks prior to enrollment.
- •Resolution of clinically significant side effects of prior chemotherapy, radiotherapy, immunotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE) Grade less than or equal to 1 or grade less than or equal to 2 for neuropathy.
- •Adequate hematologic function at screening, as follows:
- •Absolute neutrophil count (ANC) >= 1 x 10^9/L
- •Hemoglobin >= 9 g/dL
- •Platelets >= 75,000/mcL.
- •Adequate renal and hepatic function at screening, as follows:
- •Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula below):
- •Female CrCl = ((140 - age in years) x weight in kg x 0.85) / (72 x serum creatinine in mg/dL)
- •Male CrCl = ((140 - age in years) x weight in kg x 1.00)/ 1.00) / (72 x serum creatinine in mg/dL)
- •Bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 x ULN
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN, unless liver metastases are present, then values must be less than or equal to 3 x ULN)
- •The effects of the combination ETBX-011, ETBX-051, ETBX-061 vaccine regimen on the developing human fetus are unknown. For this reason, female subjects of childbearing potential defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or who is not postmenopausal (menopause being defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes) and male patients who are not surgically sterile (vasectomy etc.), must agree to use acceptable contraceptive methods for the duration of the study and for one month after the last vaccination. Acceptable forms of contraception include oral contraceptives, intrauterine device, condom or vaginal diaphragm plus spermicidal (gel/foam/cream/vaginal suppository), or total abstinence.
- •Ability to attend required study visits and return for adequate follow up, as required by this protocol.
排除标准
- •Pregnant and nursing women. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with combination ETBX-011, ETBX-051, ETBX-061, breastfeeding should be discontinued if the mother is treated with combination ETBX-011, ETBX-051, ETBX-
- •These potential risks may also apply to other agents used in this study.
- •There should be a minimum of 4 weeks from any prior investigational drug, chemotherapy, immunotherapy, with the exception of hormonal therapy for prostate and breast cancers, human epidermal growth factor receptor 2 (HER2-) directed therapy for HER2+ breast or stomach cancer (3+ immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH+), drugs targeting epidermal growth factor receptor (EGFR), anaplastic large-cell lymphoma kinase (ALK) or ROS1 in EGFR,ALK, ROS1-mutated lung cancer, respectively, or standard maintenance therapies for any solid tumor under the condition that subjects are on these therapies for at least two months before start of trial treatment.
- •There should also be a minimum of 4 weeks from any prior radiotherapy except for palliative bone directed therapy.
- •Known active brain or central nervous system metastasis (less than 1 month out from definitive radiotherapy or surgery), or seizures requiring anticonvulsant treatment, or clinically significant cerebrovascular accident or transient ischemic attack (<3 months).
- •Subjects with active autoimmune disease requiring systemic immunosuppressive treatment within the past 4 weeks such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. A history of autoimmune disease which is not active nor has required recent systemic immunosuppressive therapy (< 4 weeks prior to enrollment) is not reason for exclusion.
- •Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment.
- •Subjects with clinically significant heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly controlled angina, or history (< 1 year) of ventricular arrhythmia.
- •Subjects with a medical or psychological impediment that would impair the ability of the subject to receive therapy per protocol or impact ability to comply with the protocol or protocol-required visits and procedures.
- •History of second malignancy within 3 years prior to enrollment except for the following: adequately treated non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer or other localized malignancy after discussion with the medical monitor.
- •Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV, as determined by hepatitis B surface antigen (HBsAg) and hepatitis C serology).
- •Subjects on systemic intravenous or oral corticosteroid therapy with the exception of physiologic doses of corticosteroids (less than or equal to the equivalent of prednisone 10 mg/day) or other immunosuppressives such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these subjects these excluded treatments must be discontinued at least 2 weeks prior to enrollment for recent short course use (less than or equal to 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (> 14 days). In addition, the use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study.
- •Subjects with known allergy or hypersensitivity to any component of the investigational product will be excluded.
- •Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.
- •Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist(R)) or a killed (inactivated)/subunit vaccine (e.g., PNEUMOVAX(R), Fluzone(R)) within 28 days or 14 days, respectively, of the first planned dose of ETBX vaccine.
研究组 & 干预措施
1/Arm 1-Dose De-Escalation
Dose De-Escalation
干预措施: ETBX-051; adenoviral brachyury vaccine (Biological)
1/Arm 1-Dose De-Escalation
Dose De-Escalation
干预措施: ETBX-061; adenoviral Mucin-1 (MUC1) vaccine (Biological)
1/Arm 1-Dose De-Escalation
Dose De-Escalation
干预措施: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine (Biological)
2/Arm 2 - Dose Expansion
Dose Expansion
干预措施: ETBX-051; adenoviral brachyury vaccine (Biological)
2/Arm 2 - Dose Expansion
Dose Expansion
干预措施: ETBX-061; adenoviral Mucin-1 (MUC1) vaccine (Biological)
2/Arm 2 - Dose Expansion
Dose Expansion
干预措施: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine (Biological)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: RP2D was based upon evaluation of DLTs. Participants were followed for DLTs from the first dose of vaccine for 3 weeks.
RP2D is defined as ≤ 1 of 6 of the initial 6 subjects who experience a dose limiting toxicity (DLT), than this dose level will be defined as the RP2D. A DLT is defined as any Grade 3 or greater toxicity that is possibly related to the vaccine and as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 with the exception of transient (≤ 24 hours) Grade 3 flu-like symptoms or fever, which is controlled with medical management (≤ 24 hours) Grade 3 fatigue, skin reactions or rash, headache, nausea, emesis that resolves to Grade ≤ 1 or asymptomatic grade 3 amylase/lipase elevation.
Number of Participants With Serious and Non-serious Adverse Events
时间窗: Date treatment consent signed to date off study, approximately 16 months and 6 days.
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
次要结局
- Number of Participants Who Achieve an Objective Confirmed Complete or Partial Response Assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(Approximately 3.5 months)
- Number of Patients With Disease Control (Confirmed Response or Stable Disease (SD)) Lasting for at Least 6 Months(up to 6 months)
- Progression-free Survival (PFS)(up to 12 months)
- Overall Survival (OS)(up to 12 months)
研究者
Julius Strauss, M.D.
National Cancer Institute
National Cancer Institute (NCI)