A Phase I/IIb Study of Recombinant ALVAC(2)-NY-ESO-1 (M)/TRICOM in Combination With INCB024360 for Patients in Remission With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- PFS (Phase IIb)
研究概览
简要总结
This partially randomized phase I/IIb trial studies the side effects vaccine therapy and indoleamine 2,3-dioxygenase (IDO1) inhibitor 4-amino-1,2,5-oxadizaole-3-carboximidamide (INCB024360) and to see how well they work in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in remission. Vaccines made from gene-modified virus may help the body build an effective immune response to kill tumor cells. IDO1 inhibitor INCB024360 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vaccine therapy with IDO1 inhibitor INCB024360 may be an effective treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety of fixed doses of the modified canarypox vector (ALVAC[2])-cancer/testis antigen 1B (NY-ESO-1) (M)/triad of costimulatory molecules (TRICOM) vaccine in combination with INCB024360 (IDO1 inhibitor INCB024360). (Phase I) II. To evaluate toxicity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. (Phase I) III. To determine the progression free survival (PFS) using standard imaging response (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) criteria. (Phase IIb)
SECONDARY OBJECTIVES:
I. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity in peripheral blood NY-ESO-1 specific CD8+ and CD4+ T cells.
II. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity in peripheral blood NY-ESO-1 specific antibodies.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and no evidence of disease or no measurable disease after 1st or 2nd line therapy; 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 reverse transcription-polymerase chain reaction (RTPCR)
- •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 count (PLT) >= 75,000/uL
- •Hemoglobin (Hgb) >= 8g/dL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Serum aspartate aminotransferase (serum glutamic oxalacetic transaminase [SGOT]/aspartate aminotransferase [AST]) or serum alanine aminotransferase (serum glutamate pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) =< 3 x ULN
- •Serum creatinine =< 2 x ULN
- •Prothrombin time (PT)/international normalized ratio (INR) =< 1.5
- •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
- •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; patients who received maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have discontinued therapy (at least 4 weeks for prior taxane) prior to randomization and recovered from toxicities to less than grade 2
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 autoimmune disease (e.g. thyroiditis, lupus) except vitiligo
- •Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, and other platelet inhibitory agents
- •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
- •Clinically significant heart disease (New York Heart Association [NYHA] class III or class IV) within 6 months
- •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 human immunodeficiency virus (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
- •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 judgement, increase the patient's risk by participating in this study)
研究组 & 干预措施
Arm B (IDO1 inhibitor INCB024360)
Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: IDO1 inhibitor INCB024360 (Drug)
Arm B (IDO1 inhibitor INCB024360)
Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: laboratory biomarker analysis (Other)
Arm B (IDO1 inhibitor INCB024360)
Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: pharmacological study (Other)
Arm C (vaccine, IDO1 inhibitor INCB024360)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine (Biological)
Arm C (vaccine, IDO1 inhibitor INCB024360)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: IDO1 inhibitor INCB024360 (Drug)
Arm C (vaccine, IDO1 inhibitor INCB024360)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: laboratory biomarker analysis (Other)
Arm C (vaccine, IDO1 inhibitor INCB024360)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor INCB024360 PO BID on days 1-28.
干预措施: pharmacological study (Other)
Arm D (vaccine)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1.
干预措施: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine (Biological)
Arm D (vaccine)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1.
干预措施: laboratory biomarker analysis (Other)
Arm D (vaccine)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1.
干预措施: pharmacological study (Other)
结局指标
主要结局
PFS (Phase IIb)
时间窗: Up to 15 years
The primary analysis will be carried forth using a Cox proportional hazards model with factors corresponding to treatment combination, IDO1 inhibitor INCB024360 (yes/no) and ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine (yes/no), a continuous covariate adjustment for the length of the treatment free interval and a blocking factor.
Maximum tolerated dose of IDO1 inhibitor INCB024360, determined by incidence of dose limiting toxicities graded according to the NCI CTCAE version 4.0 (Phase I)
时间窗: 28 days
次要结局
- Immunological response(Up to 12 months)
- Toxicity rate, graded according to NCI CTCAE version 4.0(Up to 12 months)