A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- MTD of IFN-alpha-2b, defined as the dose level one level beneath that dose at which 2 or more of 6 patients showed DLT, graded according to NCI CTCAE version 4.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of interferon alfa-2b when given together with vaccine therapy and GM-CSF in treating patients with locally advanced or metastatic cancer that makes CEA. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells that make carcinoembryonic antigen (CEA). Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. Interferon alfa-2b may interfere with the growth of cancer cells and slow cancer growth. Giving vaccine therapy together with GM-CSF and interferon alfa-2b may kill more cancer cells that make CEA.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of interferon alfa-2b (IFN-α-2b) when administered with recombinant vaccinia-CEA(6D)-TRICOM vaccine, recombinant fowlpox-CEA(6D)-TRICOM vaccine, and sargramostim (GM-CSF) in patients with locally advanced or metastatic carcinoembryonic antigen (CEA)-expressing carcinoma.
SECONDARY OBJECTIVES:
I. Determine the effect of IFN-α-2b on tumor cell expression of CEA and MHC class I antigens in patients treated with this regimen.
II. Determine the immunologic effects of this regimen in these patients. III. Determine any objective anti-tumor responses that may occur in response to this regimen in these patients.
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
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
- •Histologically confirmed carcinoembryonic antigen (CEA)-expressing carcinoma
- •Metastatic or locally advanced disease
- •Tumor accessible for biopsy
- •Must have received ≥ 1 prior systemic regimen for metastatic disease
- •No known brain metastases
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 6 months
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 2.0 times upper limit of normal (ULN)
- •AST and ALT ≤ 4.0 times ULN
- •Hepatitis B negative
- •Hepatitis C negative
- •Creatinine ≤ 1.96 mg/dL
- •Creatinine clearance > 50 mL/min
- •No persistent proteinuria
- •Protein < 1,000 mg by 24-hour urine collection
- •No urinary sediment abnormalities
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No clinically significant cardiomyopathy requiring treatment
- •No impaired function (i.e., ejection fraction < 50%) for patients who have not had prior vaccine and are asymptomatic
- •HIV negative
- •No ongoing or active infection
- •No history of allergic reaction to eggs or egg products
- •No history of allergy or untoward reaction to prior vaccinia vaccination (e.g., smallpox immunization) or to any of its components
- •No history of or active eczema or other eczematoid skin disorders
- •No atopic dermatitis
- •No other acute, chronic, or exfoliative skin conditions, including any of the following:
- •Varicella zoster
- •Severe acne
- •Other open wounds or rashes
- •No immunocompromised condition
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- •No sexual contact for 3 weeks after each vaccination treatment
- •Must be willing to undergo tumor biopsy
- •No psychiatric illness or social situation that would preclude study compliance
- •No life-threatening illness
- •No other active malignancy within the past 2 years except nonmelanoma skin cancer or superficial bladder or cervical lesions treated with surgical resection
- •No other uncontrolled illness
- •Must be able to avoid close household contact with the following individuals for ≥ 3 weeks after vaccinia vaccination:
- •Pregnant or nursing women
- •Children under 5 years of age
- •Individuals who are immunodeficient or immunosuppressed by disease or therapy (including HIV infection)
- •Individuals with the following conditions:
- •History of or active eczema or other eczematoid skin disorders
- 另有 10 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients who do not have progressive disease or unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
干预措施: Recombinant Fowlpox-CEA(6D)/TRICOM Vaccine (Biological)
Arm I
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients who do not have progressive disease or unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
干预措施: Recombinant Vaccinia-CEA(6D)-TRICOM Vaccine (Biological)
Arm I
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients who do not have progressive disease or unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
干预措施: Sargramostim (Biological)
Arm I
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients who do not have progressive disease or unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
干预措施: Recombinant Interferon Alfa-2b (Biological)
结局指标
主要结局
MTD of IFN-alpha-2b, defined as the dose level one level beneath that dose at which 2 or more of 6 patients showed DLT, graded according to NCI CTCAE version 4.0
时间窗: Up to 112 days
次要结局
- Response to treatment, evaluated using the new international criteria proposed by the RECIST Committee(Up to 15 years)
- Incidence of adverse events, graded according to NCI CTCAE version 4.0(Up to 15 years)