Randomized Single Institution Pilot Study of Vaccinia-CEA(6D)-TRICOM and Fowlpox-CEA(6D)-TRICOM With GM-CSF in Combination With Docetaxel in Patients With CEA-Bearing Cancers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Immune response defined as the numbers of patients who achieve an ELISPOT result of 1/30,000 or higher divided by the number of HLA-A2 positive individuals for each treatment arm
研究概览
简要总结
This randomized phase I trial studies the side effects, best way to give, and best dose of docetaxel when given together with vaccine therapy and sargramostim in treating patients with metastatic lung cancer or metastatic colorectal cancer. Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow and peripheral blood. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy and sargramostim with docetaxel may kill more tumor cells.
详细描述
OBJECTIVES:
I. Determine the recommended dose and schedule of docetaxel when given in combination with recombinant vaccinia-CEA-TRICOM vaccine, recombinant fowlpox-CEA-TRICOM vaccine, and sargramostim (GM-CSF), defined by best immune response with acceptable toxicity, in patients with carcinoembryonic antigen (CEA)-expressing metastatic lung or colorectal cancer.
II. Compare the effect of varying doses and schedules of docetaxel on CEA-specific T-cell immune responses by ELISPOT assay in patients treated with these regimens.
III. Compare objective antitumor response in patients treated with these regimens.
OUTLINE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 lung OR colorectal cancer
- •Incurable metastatic disease
- •Currently available standard treatment not likely to offer a survival advantage or result in superior palliation
- •Evaluable disease by radiograph
- •Tumor must currently express carcinoembryonic antigen (CEA) by immunohistochemistry OR CEA >= 10 ng/mL at any point during disease course
- •No clinically active brain metastases
- •Must have had first- and second-line treatment OR declined second-line treatment (part I only)
- •Patients with colon cancer must have had or have been offered treatment with oxaliplatin (part I only)
- •Life expectancy of at least 4 months
- •Absolute neutrophil count >= 1,500/mm^3
- •WBC >= 3,000/mm^3
- •Platelet count >= 100,000/mm^3
- •Bilirubin normal
- •Meets 1 of the following criteria:
- •SGOT and SGPT =< 2.5 times upper limit of normal (ULN) AND alkaline phosphatase normal
- •SGOT and SGPT =< normal AND alkaline phosphatase =<4.0 times ULN
- •Hepatitis B and C negative by clinical history and physical exam
- •Creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 mL/min
- •Proteinuria =< grade 1
- •No known or suspected history of impaired cardiac function as evidenced by baseline echocardiogram
- •Adequate pulmonary function
- •No history or clinical evidence of immune deficiency or autoimmunity
- •HIV negative
- •No history of or concurrent diagnosis of any of the following:
- •Altered immunodeficiency
- •Eczema or other eczematoid skin disorders
- •Acute, chronic, or exfoliative skin condition (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
- •No history of allergy or untoward reaction to prior vaccination with vaccinia virus
- •No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
- •No history of allergy to eggs or egg products
- •No frequent vomiting or severe anorexia
- •No inflammatory bowel disease
- •No Crohn's disease
- •No ulcerative colitis
- •No active diverticulitis
- •Neuropathy =< grade 1 (sensory neuropathy)
- •No uncontrolled seizure disorder
- •No encephalitis
- •No multiple sclerosis
- •Must be maintaining a reasonable state of nutrition (=< 10 % weight loss in the past month)
- •Must be able to avoid close household contact (defined as sharing housing or having close physical contact) for at least 3 weeks after recombinant vaccinia vaccination with individuals with active or a history of eczema or other eczematoid skin disorders
- •Must be able to avoid close household contact (defined as sharing housing or having close physical contact) for at least 3 weeks after recombinant vaccinia vaccination with those with unresolved acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
- •Must be able to avoid close household contact (defined as sharing housing or having close physical contact) for at least 3 weeks after recombinant vaccinia vaccination with any of the following individuals: pregnant or nursing women; children =< 5 years of age; immunodeficient or immunosuppressed individuals (by disease or therapy), including HIV infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for at least 6 months after study participation
- •No other concurrent serious medical illness that would preclude study participation
- •No concurrent biologic therapy
- •No other concurrent immunotherapy
- •At least 6 weeks since prior nitrosoureas or mitomycin
- 另有 14 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
Three weeks after treatment with vaccinia-CEA-TRICOM vaccine, patients receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC into each vaccination site on days 1-4.
干预措施: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Drug)
Arm I
Three weeks after treatment with vaccinia-CEA-TRICOM vaccine, patients receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC into each vaccination site on days 1-4.
干预措施: recombinant vaccinia-CEA(6D)-TRICOM vaccine (Drug)
Arm I
Three weeks after treatment with vaccinia-CEA-TRICOM vaccine, patients receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC into each vaccination site on days 1-4.
干预措施: sargramostim (Drug)
Arm II
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and lower-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Drug)
Arm II
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and lower-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: recombinant vaccinia-CEA(6D)-TRICOM vaccine (Drug)
Arm II
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and lower-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: docetaxel (Drug)
Arm II
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and lower-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: sargramostim (Drug)
Arm IV
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and full-dose docetaxel IV over 1 hour on day 1.
干预措施: recombinant vaccinia-CEA(6D)-TRICOM vaccine (Drug)
Arm III
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and standard-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Drug)
Arm III
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and standard-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: recombinant vaccinia-CEA(6D)-TRICOM vaccine (Drug)
Arm III
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and standard-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: docetaxel (Drug)
Arm III
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and standard-dose docetaxel IV over 30 minutes on days 1 and 8.
干预措施: sargramostim (Drug)
Arm IV
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and full-dose docetaxel IV over 1 hour on day 1.
干预措施: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Drug)
Arm IV
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and full-dose docetaxel IV over 1 hour on day 1.
干预措施: docetaxel (Drug)
Arm IV
Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and full-dose docetaxel IV over 1 hour on day 1.
干预措施: sargramostim (Drug)
Arm V
Patients receive full-dose docetaxel IV over 1 hour on day 1, fowlpox-CEA-TRICOM vaccine SC on day 8, and GM-CSF SC into each vaccination site on days 8-11.
干预措施: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Drug)
Arm V
Patients receive full-dose docetaxel IV over 1 hour on day 1, fowlpox-CEA-TRICOM vaccine SC on day 8, and GM-CSF SC into each vaccination site on days 8-11.
干预措施: recombinant vaccinia-CEA(6D)-TRICOM vaccine (Drug)
Arm V
Patients receive full-dose docetaxel IV over 1 hour on day 1, fowlpox-CEA-TRICOM vaccine SC on day 8, and GM-CSF SC into each vaccination site on days 8-11.
干预措施: docetaxel (Drug)
Arm V
Patients receive full-dose docetaxel IV over 1 hour on day 1, fowlpox-CEA-TRICOM vaccine SC on day 8, and GM-CSF SC into each vaccination site on days 8-11.
干预措施: sargramostim (Drug)
Arm VI
Patients receive full-dose docetaxel as in arm V, fowlpox-CEA-TRICOM vaccine SC on day 15, and GM-CSF SC into each vaccination site on days 15-18.
干预措施: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Drug)
Arm VI
Patients receive full-dose docetaxel as in arm V, fowlpox-CEA-TRICOM vaccine SC on day 15, and GM-CSF SC into each vaccination site on days 15-18.
干预措施: recombinant vaccinia-CEA(6D)-TRICOM vaccine (Drug)
Arm VI
Patients receive full-dose docetaxel as in arm V, fowlpox-CEA-TRICOM vaccine SC on day 15, and GM-CSF SC into each vaccination site on days 15-18.
干预措施: docetaxel (Drug)
Arm VI
Patients receive full-dose docetaxel as in arm V, fowlpox-CEA-TRICOM vaccine SC on day 15, and GM-CSF SC into each vaccination site on days 15-18.
干预措施: sargramostim (Drug)
结局指标
主要结局
Immune response defined as the numbers of patients who achieve an ELISPOT result of 1/30,000 or higher divided by the number of HLA-A2 positive individuals for each treatment arm
时间窗: Up to 6 years
The actual ELISPOT will be recorded for each individual and will be presented graphically.
Number of patients experiencing each of the toxicities by grade for each treatment arm
时间窗: Up to 6 years
Anti-tumor response rate defined as the number of patients in each arm achieving a complete or partial response or stable disease divided by the total number of patients on each arm measured according to standard RECIST guidelines
时间窗: Up to 6 years
次要结局
- Average quantity of circulating CEA cells determined by quantitative real time RT-PCR(Up to 6 years)