A PHASE 2 EFFICACY TRIAL OF INTENSIVE LOCOREGIONAL CHEMOIMMUNOTHERAPY FOR ADVANCED STAGE OVARIAN CANCER AND TUMOR-SPECIFIC INTRANODAL AUTOLOGOUS ALPHA-DC1 VACCINES
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Number of adverse events for the different combinations
研究概览
简要总结
This study will evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) at primary neoadjuvant setting.
In the safety phase I phase, we determined the tolerable dose of IPC-CKM. In this phase 2 we will add intradermal (ID) autologous αDC1 vaccines (known to be nontoxic) to the tolerable IPC-CKM regimen. The effectiveness will be determined by rate of complete pathologic response.
详细描述
On Phase 1, patients received up to 6 cycles of IPC, with CKM after the 2nd to 6th cycles. On Phase 2, (which opened 8/27/24/ )patients will receive up to 6 -8 cycles of chemotherapy with ID injections of DC1 vaccine with CKM. To optimize the pattern of immunity, all patients will also receive oral celecoxib (COX2 inhibitor).
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
- •Patients must have advanced stage (III-IV) epithelial carcinoma of ovarian, tubal, or peritoneal origin.
- •Histologic documentation of the original primary tumor is required via the pathology report.
- •Original tumor blocks from primary diagnosis biopsy will be reviewed by our study pathologist at Magee.
- •Patients must be receiving neoadjuvant chemotherapy
- •Patients must be eligible for cancer-related definitive therapy with neoadjuvant chemotherapy
- •Patients must be chemonaive and receiving therapy in primary first line neoadjuvant setting
- •Patients must have GOG performance of 0-1
- •Patients must be reasonable candidates for interval debulking surgery as well as IP platinum based combination chemotherapy regimen with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal toxicity, or bowel obstruction.
- •Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to the first date of treatment on this study.
- •Patient must be willing to undergo leukapheresis
- •Patients must agree to appropriate clinical monitoring to receive the study regimens.
- •Patient must have:
- •Bone marrow function:
- •Absolute neutrophil count (ANC) greater than or equal to 1,500/µL, equivalent to CTCAE v4 grade
- •Platelets greater than or equal to 100,000/µL;
- •hemoglobin greater than or equal to 8.0 g/dL.
- •Renal function:
- •creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4 grade
- •Hepatic function:
- •Bilirubin less than or equal to 1.5 x ULN (CTCAE v4 grade 1).
- •SGOT and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4 grade 1).
- •Patients who have signed informed consent and authorization permitting release of personal health information.
- •Patients must have a GOG Performance Status of 0 or
排除标准
- •Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).
- •Patients with a known allergy to cisplatin or taxane chemotherapy. Patients with carboplatin allergy may be included if they tolerate a test dose of IV cisplatin given in monitored floor conditions. Patients who are allergic to paclitaxel, can be alternatively treated with abraxane.
- •Patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.
- •Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies.
- •Patients with uncontrolled diseases other than cancer will be excluded.
- •Patients who are pregnant or nursing.
- •Patients who have contraindications to the use of NSAID's like chronic renal failure, coronary artery disease, or bleeding ulcers.
- •Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with no peritoneal disease.
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- •Patients with previous pelvic radiation therapy.
研究组 & 干预措施
Cisplatin + Celecoxib + DC Vaccine
Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + intranodal vaccine injections once per cycle
干预措施: Cisplatin + celecoxib + DC vaccine (Biological)
Cisplatin + CKM + Celecoxib + DC Vaccine
Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + IFN by IP once per cycle + rintatolimod 200 mg by IP once per cycle + intranodal vaccine injections once per cycle
干预措施: Cisplatin + CKM + Celecoxib + DC Vaccine (Biological)
结局指标
主要结局
Number of adverse events for the different combinations
时间窗: 8 weeks
2 patients will be treated and observed for 2 cycles on each of the dose tiers to identify the acceptable dose of IFN in combination with the other protocol drugs/vaccine for the second phase of the trial.
Change in the number of CD8+ tumor infiltrating T cells in the peritoneal fluid.
时间窗: 8 weeks
The difference in CD8+ tumor infiltrating T cells over 3 cycles of platinum based chemotherapy plus immunotherapy compared with baseline.
次要结局
- Change in the number of Tregs in the peritoneal fluid.(8 weeks)
- Change in the number of effector CD8+ T cells in the peritoneal fluid.(8 weeks)
- Change in the number of CD3+CD8+ T cells in the peritoneal fluid.(8 weeks)
- Change in the number of CD4+ T cells in the peritoneal fluid.(8 weeks)
- Change in the number of myeloid-derived suppressor cells in the peritoneal fluid.(8 weeks)