IMMUNOCERV: Evaluating the Safety of Chemoradiation Combined With PDS0101 Immunotherapy in Treating Locally Advanced Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Rate of grade >= 3 acute toxicity
研究概览
简要总结
This phase IIA trial studies the effect of a vaccine (PDS0101) when given together with chemotherapy and radiation therapy (chemoradiation) in treating patients with stage IB3-IVA cervical cancer. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. PDS0101 is a type of vaccine that is intended to help the immune system respond to human papillomavirus (HPV16)-infected cervical tumor cells. PDS0101 contains two active components: the first is called R-DOTAP (Versamune) and is included in the vaccine to boost the immune system's response against the HPV viral proteins and the second group of active components are selected small pieces of proteins (called peptides) taken from the HPV virus. Giving PDS0101 in combination with chemoradiation may work help to control cervical cancer.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate the safety and toxicity profile of delivering the immune nanoparticle liposomal HPV-16 E6/E7 multipeptide vaccine PDS0101 (PDS0101) with standard-of-care chemoradiation (chemoRT) in patients with locally advanced cervical cancer.
SECONDARY OBJECTIVES:
I. Rate of complete metabolic response on day 170 (+/- 14 days) positron emission tomography computed tomography (PET CT).
II. Rate of >= 90% gross tumor volume reduction day 35 magnetic resonance imaging (MRI) (+/- 5 days).
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
- •Age 18 years or older
- •Newly diagnosed locally advanced squamous cell carcinoma of cervix (FIGO 2018 stage IB3-IVA with primary tumor ≥ 5 cm and/or positive pelvic or periaortic nodal disease assessed by imaging).
- •Histologic diagnosis of squamous cell carcinoma of the cervix.
- •Written informed consent before initiation of any study-related procedures;
- •WHO/ECOG performance status 0-
- •Adequate liver (ALT, AST, Alk Phos and total Bili ≤ 2-fold the upper limit of normal), and renal functions (Creatinine ≤ 1.5).
- •Absence of current malignancies at other sites, except for adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors who have undergone potentially curative therapy for a prior malignancy who have no evidence of that disease for 5 years and who are deemed at low risk for recurrence are eligible for the study
排除标准
- •HIV infection, cellular immune deficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
- •Prior diagnosis of hepatitis B or C (unless anti-hepatitis C therapy has produced a sustained virologic response);
- •History of clinically significant autoimmune disease, Crohn's disease, or ulcerative colitis
- •Serious concomitant disorder, including active systemic infection requiring treatment, as judged by the Investigator.
- •Receipt of immunotherapy (e.g., IFNs, check-point inhibitors, tumor necrosis factor, interleukins, etc.) or biological response modifiers (GM-CSF, granulocyte colony-stimulating factor, macrophage colony-stimulating factor) within 4 weeks before the first study vaccination.
- •Receipt of chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- •Current or recent use of physiologic doses of intra-articular, topical, or inhaled corticosteroids is acceptable.
- •History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines [e.g., Silgard®, Cervarix®, Gardasil®] are not excluded)
- •Known or suspected hypersensitivity to any component of the investigational product or contraindications to cisplatin (e.g., peripheral neuropathy grade ≤ 2 or ototoxicity ≤grade 2 per CTCAE v5.0)
- •Previous pelvic RT.
- •Previous chemotherapy for the cervix tumor
- •Previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy
- •Prior major surgery within 4 weeks of enrollment from which the patient has not recovered
- •Other condition or prior therapy that, in the opinion of the Investigator, compromises the subject's welfare or may confound study results
- •Concurrent participation in another therapeutic investigational study or use of another investigational drug within 6 months before the first study vaccination
- •Previous enrollment in this study
- •HPV genotyping is to be done from cervical swab samples. Enrollment will not require HPV testing.
- •Pregnancy: a female subject defined as a WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
研究组 & 干预措施
Treatment (radiation therapy, cisplatin, PDS0101)
Patients undergo radiation therapy over 1 hour 5 days per week (Monday-Friday) for 5-7 weeks and receive cisplatin IV over 4 hours QW during the 5 weeks of radiation therapy in the absence of disease progression and unacceptable toxicity. Patients also receive PDS0101 SC on days -10, 7, 28, 49, and 170 in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Treatment (radiation therapy, cisplatin, PDS0101)
Patients undergo radiation therapy over 1 hour 5 days per week (Monday-Friday) for 5-7 weeks and receive cisplatin IV over 4 hours QW during the 5 weeks of radiation therapy in the absence of disease progression and unacceptable toxicity. Patients also receive PDS0101 SC on days -10, 7, 28, 49, and 170 in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Treatment (radiation therapy, cisplatin, PDS0101)
Patients undergo radiation therapy over 1 hour 5 days per week (Monday-Friday) for 5-7 weeks and receive cisplatin IV over 4 hours QW during the 5 weeks of radiation therapy in the absence of disease progression and unacceptable toxicity. Patients also receive PDS0101 SC on days -10, 7, 28, 49, and 170 in the absence of disease progression or unacceptable toxicity.
干预措施: Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101 (Biological)
结局指标
主要结局
Rate of grade >= 3 acute toxicity
时间窗: Day -10 to day 80
Measured from first vaccine injection up to 30 days following completion of chemoradiotherapy (chemoRT). Adverse events (AEs) will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Any AE that occurs between the first day of PDS0101 injection and up to 30 days following completion of chemoRT (\~Day 80) will be considered as acute toxicity (AT).
次要结局
- Rate of complete metabolic response(Day 170)
- Rates of overall survival(At 12 and 18 months)
- Rate of grade >= 3 chronic toxicity(Day 81 to completion of trial)
- Rates of local control(At 12 and 18 months)
- Rate of >= 90% gross tumor volume reduction(Day 35)
- Rates of progression-free survival(At 12 and 18 months)