A Phase 2 Study of Pembrolizumab (MK-3475), DPX-Survivac Vaccine and Low Dose of Cyclophosphamide Combination in Patients With Advanced Ovarian, Primary Peritoneal or Fallopian Tube Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This is a phase 2 study whose purpose is to see whether the combination of of pembrolizumab, DPX-Survivac vaccine and low-dose cyclophosphamide has anti-tumor activity in patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer.
DPX-Survivac is an investigational vaccine. A vaccine is a substance that is often given to stimulate the body's immune system (the structure and processes in the body that protects against harmful substances) to help prevent against certain diseases. DPX-Survivac is a vaccine that may teach the immune system to recognize cancer cells and to kill them.
Pembrolizumab is a drug that is approved for the treatment of a certain type of melanoma (a type of skin cancer) and non-small cell lung cancer. Pembrolizumab blocks the function of a protein called programmed cell death receptor-1 (PD-1). PD-1 works by keeping the immune system from destroying cancer cells. Stopping PD-1 from working may help the immune system to fight cancer cells.
Cyclophosphamide is chemotherapy drug that is approved for the treatment of various cancers alone and in combination with other drugs.
详细描述
This study has two phases: a dose escalation phase and a dose expansion phase.
For the dose escalation part, groups of participants will receive one of two dose levels of study drugs to determine the best dose level for further testing.
Once the best dose level is found, additional participant will be enrolled to the dose expansion to further test the safety, tolerability, and efficacy of the study drugs at that dose level in specific types of cancers. All participants will receive pembrolizumab, DPX-Survivac, and low-dose cyclophosphamide.
Participants will be screened for eligibility by standard safety tests and procedures within 28 days of the start of the study drug. Tests and procedures done for research purposes only during this time include archival tumor tissue collection, fresh research biopsy, and blood sample collection for biomarker/genetic/immune research. Participants will also be asked if they agree to an optional fresh research biopsy at disease progression
Eligible participants will receive the following every 21 day cycle:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 histologically or cytologically confirmed advanced epithelial ovarian, primary peritoneal or fallopian tube carcinomas.
- •Patients must have radiologically documented disease progression from their prior line of therapy.
- •Patients must have measurable disease based on RECIST 1.
- •Have received a front line platinum-based regimen (administered via either IV or IP) following primary or interval debulking surgery with documented disease recurrence.
- •Have fulfilled the following additional requirements regarding prior treatments depending on the cohort that the patient is to be enrolled in.
- •Eastern Cooperative Group (ECOG) performance status <=
- •Life expectancy greater than 16 weeks.
- •Availability of archival tumor tissue samples. Additional samples may be requested if tumor tissue provided is not adequate for quality and/or quantity as assessed by the laboratory.
- •Be willing to provide tumor tissue from a newly obtained core or excisional biopsy prior to start treatment and on day 15 of cycle 1.
排除标准
- •Patients who are receiving any other investigational agents.
- •Diagnosis of immunodeficiency or therapy with systemic steroid or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •History of autoimmune disease, such as but not restricted to, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematous, ankylosing spondylitis, scleroderma, or multiple sclerosis requiring treatment within the last two years. Patients with vitiligo or diabetes are not excluded.
- •Patients with history of thyroiditis within 5 years.
- •Patients with known history of active TB (Bacillus Tuberculosis).
- •Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Hypersensitivity to Pembrolizumab, DPX-Survivac immunovaccine, Cyclophosphamide or any of their excipients.
- •Patients that have received a live vaccine within 30 days of planned start of study therapy.
- •Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or DPX-Survivac vaccine.
研究组 & 干预措施
Dose Escalation
Patients with epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: Pembrolizumab (Drug)
Dose Escalation
Patients with epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: DPX-Survivac (Biological)
Dose Escalation
Patients with epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: Cyclophosphamide (Drug)
Dose Expansion - Cohort A
Patients with platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: Pembrolizumab (Drug)
Dose Expansion - Cohort A
Patients with platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: DPX-Survivac (Biological)
Dose Expansion - Cohort A
Patients with platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: Cyclophosphamide (Drug)
Dose Expansion - Cohort B
Patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: Pembrolizumab (Drug)
Dose Expansion - Cohort B
Patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: DPX-Survivac (Biological)
Dose Expansion - Cohort B
Patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.
干预措施: Cyclophosphamide (Drug)
Dose Expansion - Cohort C
Patients with recurrent advanced epithelial ovarian, fallopian tube and primary peritoneal patients with uncommon tumor histologies, including clear cell, mucinous and low grade serous or low grade endometrioid ovarian subtypes.
干预措施: Pembrolizumab (Drug)
Dose Expansion - Cohort C
Patients with recurrent advanced epithelial ovarian, fallopian tube and primary peritoneal patients with uncommon tumor histologies, including clear cell, mucinous and low grade serous or low grade endometrioid ovarian subtypes.
干预措施: DPX-Survivac (Biological)
Dose Expansion - Cohort C
Patients with recurrent advanced epithelial ovarian, fallopian tube and primary peritoneal patients with uncommon tumor histologies, including clear cell, mucinous and low grade serous or low grade endometrioid ovarian subtypes.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 5 years
ORR will be used to evaluate the clinical anti-tumor activity of Pembrolizumab, DPX Survivac and oral cyclophosphamide combination.
次要结局
- Progression free survival (PFS) rate(5 years)
- Overall survival (OS) rate(5 years)
- Number of side effects(5 years)