A Phase I Clinical Trial of mTOR Inhibition With Sirolimus for Enhancing ALVAC(2)-NY-ESO-1(M)/TRICOM Vaccine Induced Anti-Tumor Immunity in Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine in combination with varying dose levels and schedules of sirolimus, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
研究概览
简要总结
This phase I trial studies the side effects and best dose and schedule of sirolimus when given together with vaccine therapy in treating patients with stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer. Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with sirolimus may be an effective treatment for ovarian, fallopian tube, or primary peritoneal cancer
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine with sirolimus at varying dose and schedule.
SECONDARY OBJECTIVES:
I. To determine the effectiveness of sirolimus on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity: peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T-cells; peripheral blood NY-ESO-1 specific antibodies; peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T-cells.
II. Explore time to disease progression.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Eligible patients will be women with stages II-IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who have completed standard therapy for primary or recurrent disease (i.e., patients who would normally be observed); eligible patients may have asymptomatic residual measurable disease on physical examination and/or computed tomography (CT) scan, and/or may have an elevated cancer antigen 125 (CA-125); or may be in complete clinical remission after treatment for primary or recurrent disease; these patients would normally enter a period of observation after standard management
- •Any human leukocyte antigen (HLA) type; (historic HLA typing is permitted)
- •Tumor expression of NY-ESO-1 or cancer/testis antigen 2 (LAGE-1) by immunohistochemistry (IHC) and/or real-time polymerase chain reaction (RT-PCR)
- •No allergy to eggs
- •Life expectancy > 6 months
- •Hematology and biochemistry laboratory results within the limits normally expected for the patient population, without evidence of major organ failure
- •Absolute neutrophil count (ANC) >= 1,000/uL
- •Platelet >= 75,000/uL
- •Hemoglobin (Hgb) >= 8 g/dL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) =< 3 x ULN
- •Serum creatinine =< 2 x ULN
- •Prothrombin time (PT)/international normalized ratio (INR) =< 1.5
- •Electrocardiogram, showing no evidence of congestive heart failure, myocardial infarction, and cardiomyopathy
- •Have been informed of other treatment options
- •Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- •Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2
- •Demonstrate the ability to swallow and retain oral medication
- •Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment
- •Patients may have received previous NY-ESO-1 vaccine therapy
排除标准
- •Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available
- •Other serious illnesses (e.g. serious infections requiring antibiotics, bleeding disorders)
- •History of severe autoimmune disorders requiring use of steroids or other immunosuppressives
- •Concomitant systemic treatment with corticosteroids, anti-histamine or nonsteroidal anti-inflammatory drugs and other platelet inhibitory agents, strong inhibitors/inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450-3A4)
- •Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study drug (6 weeks for nitrosoureas); concomitant hormonal therapies for breast cancers are allowed
- •Known allergy or history of life threatening reaction to GM-CSF
- •Clinically significant heart disease (N-YHA Class III or IV)
- •Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study drug
- •Known hepatitis B, hepatitis C, or HIV
- •Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
- •Lack of availability of a patient for immunological and clinical follow-up assessment
- •Known pulmonary hypertension
- •Known hypersensitivity to sirolimus
- •Evidence of current drug or alcohol abuse or psychiatric impairment, which in the investigator's opinion will prevent completion of the protocol therapy or follow-up
- •Pregnant or nursing female patients
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug; (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study)
研究组 & 干预措施
Treatment (vaccine, sirolimus, GM-CSF)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4. Patients also receive sirolimus PO QD on days 1-14 OR 15-28 OR 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive an additional course of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine only followed by ALVAC(2)-NY-ESO-I (M)/TRICOM vaccine SC 8 weeks after completion of course 4.
干预措施: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine (Biological)
Treatment (vaccine, sirolimus, GM-CSF)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4. Patients also receive sirolimus PO QD on days 1-14 OR 15-28 OR 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive an additional course of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine only followed by ALVAC(2)-NY-ESO-I (M)/TRICOM vaccine SC 8 weeks after completion of course 4.
干预措施: sirolimus (Drug)
Treatment (vaccine, sirolimus, GM-CSF)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4. Patients also receive sirolimus PO QD on days 1-14 OR 15-28 OR 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive an additional course of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine only followed by ALVAC(2)-NY-ESO-I (M)/TRICOM vaccine SC 8 weeks after completion of course 4.
干预措施: laboratory biomarker analysis (Other)
Treatment (vaccine, sirolimus, GM-CSF)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4. Patients also receive sirolimus PO QD on days 1-14 OR 15-28 OR 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive an additional course of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine only followed by ALVAC(2)-NY-ESO-I (M)/TRICOM vaccine SC 8 weeks after completion of course 4.
干预措施: sargramostim (Biological)
结局指标
主要结局
Safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine in combination with varying dose levels and schedules of sirolimus, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
时间窗: Up to 30 days after completion of study treatment
The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson). The lower one sided limit will be used.
次要结局
- Antibody titers(At baseline, days 29, 57, 85, 141, and at 6 weeks-post treatment)
- NY-ESO-1 specific CD8+ and CD4+ frequency and function(At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment)
- Frequency of memory T-cell populations(At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment)
- TCR avidity(At baseline, days 1, 29, 57, 85, 113, 141, and at 6 weeks-post treatment)
- Secondary recall response(Up to 1 year)
- Time to disease progression(Up to 1 year)
- Effectiveness of sirolimus on enhancing vaccine efficacy, assessed by NY-ESO-1 specific cellular and humoral immunity(Up to 1 year)