A Phase Ib/II Trial To Test The Safety And Efficacy Of Vaccination With HPV16-E711-19 Nanomer For The Treatment Of Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer In HLA-A*02 Positive Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b]
研究概览
简要总结
This research study is studying a therapeutic vaccine, named DPX-E7, as a possible treatment for Human Papilloma Virus or HPV related head and neck, cervical or anal cancer (positive for HLA-A*02).
详细描述
This is a phase Ib/II clinical trial. DPX-E7 is a therapeutic vaccine, intended to treat HPV-related head and neck, cervical or anal cancer. DPX-E7 is an investigational vaccine and the FDA (the U.S. Food and Drug Administration) has not approved DPX-E7 vaccine as a treatment for any disease.
DPX-E7 is being tested in humans for the first time. DPX-E7 is a kind of immunotherapy that will make the immune system to elicit an anti-tumor response by generating CD8+ T-cells. CD8+ T-cells play a very important role in fighting against viral infections
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Each patient must be positive for HLA-A*02 and meet all of the following inclusion criteria to be enrolled in the study:
- •Histologically or cytologically proven HPVOC or cervical cancer or anal cancer, based on expression of HPV type16 in immunohistochemistry and/or HPV 16 DNA analysis by ISH of tumor tissue from the primary or metastatic lesions.
- •Incurable HPVOC, as defined by:
- •Relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment (e.g. Surgery, radiotherapy or chemoradiotherapy) with no potentially curative option (i.e. surgery or radiation); OR
- •Distant metastasis
- •Incurable cervical or anal cancer, as defined by:
- •Relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment (e.g. systemic chemotherapy) with no potentially curative option (i.e. surgery or chemoradiotherapy). Chemotherapy administered in conjunction with primary radiation as a radiosensitizer will not be counted as a systemic chemotherapy regimen; OR
- •Distant metastasis refractory to initial treatment (at least one prior chemotherapeutic regimen which can include a single chemotherapeutic, a combination of chemotherapeutics, or biologic drugs such as bevacizumab).
- •Accessible tumors for sequential biopsies Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.03) to grade 1 or better (except for < grade 2 neuropathy, alopecia, xerostomia, dysphagia, or mucositis);
- •Age ≥ 18 years;
- •Measurable disease, according to modified RECIST 1.1 and irRECIST (Appendix B & C);
- •Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 (Appendix A)
- •Adequate bone marrow, liver and renal function, defined by:
- •Hemoglobin ≥ 10 g/dL;
- •Absolute neutrophil count (ANC) ≥ 1000/μL;
- •Absolute lymphocyte count ≥ 400/μL;
- •Platelet count ≥ 100,000/μL;
- •ALT and AST ≤ 2.5 X upper limit of normal (ULN);
- •Total bilirubin ≤ 1.5 X ULN; and
- •Serum creatinine ≤ 1.5 X ULN;
- •Women of child-bearing potential (WOCBP) must be willing to use acceptable means of birth control;
- •Men who could potentially father a child must also use birth control
- •Signed informed consent
排除标准
- •Radiotherapy for primary HPVOC within 8 weeks, or radiotherapy for any other reason within 3 weeks prior to the first dose of trial treatment;
- •Chemotherapy within 3 weeks prior to the first dose of trial treatment;Other cancer in the past 5 years, except for carcinoma in situ of the cervix or bladder, or non-melanomatous skin cancer;
- •Inaccessible tumor or lack of consent for sequential biopsies
- •Uncontrolled central nervous system (CNS) metastases (i.e. known CNS lesions that are radiographically unstable, symptomatic and/or requiring escalating doses of corticosteroids);
- •Active hepatitis, known HIV, or other condition that requires immunosuppressive therapy, including current use of high dose systemic corticosteroids;
- •Autoimmune disease, such as systemic lupus erythematosis or rheumatoid arthritis, that is active and requires current immunosuppressive therapy;
- •Active uncontrolled serious infection;
- •WOCBP who have a positive β-hCG test or are breastfeeding.
- •Acute or chronic skin disorders that would interfere with subcutaneous injection of the vaccine or subsequent assessment of potential skin reactions;
- •Allergies to any vaccine, that after discussion with Immunovaccine, are serious enough to warrant exclusion from this study
研究组 & 干预措施
DPX-E7 + Cyclophosphamide [Phase Ib Cohort]
Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression.
干预措施: DPX-E7 vaccine (Drug)
DPX-E7 + Cyclophosphamide [Phase Ib Cohort]
Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression.
干预措施: Cyclophosphamide (Drug)
DPX-E7 + Cyclophosphamide [Phase II Cohort 1]
Participants were enrolled before amendment 10. Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression.
干预措施: DPX-E7 vaccine (Drug)
DPX-E7 + Cyclophosphamide [Phase II Cohort 1]
Participants were enrolled before amendment 10. Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression.
干预措施: Cyclophosphamide (Drug)
DPX-E7 [Phase II Cohort 2]
Participants were enrolled after amendment 10. Participants received two 0.50 mL priming doses of DPX-E7 3 weeks apart, followed by 0.2 mL booster dose every 8 weeks until clinical progression.
干预措施: DPX-E7 vaccine (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b]
时间窗: Patients were followed for 50 days.
A DLT was defined as any grade 3 or greater adverse event at least possibly related to the study agent including injection site reactions; or grade 2 or greater allergic reactions which occur in a subject prior to day 50, will trigger DLT. In addition, to be considered as DLT, the adverse event must be considered at least possibly related to study treatment. Grade 3 or greater abnormal lab values lasting \<= 72 hours might be excluded as DLTs if there are no accompanying clinical signs and symptoms per investigator's discretion.
Grade 1-2 Treatment-Related AE Rate
时间窗: The median follow up was 2.92 months (range 1.25 - 5.88months).
The proportion of participants who experienced grade 1-2 treatment-related adverse events based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) as reported on case report forms.
Changes in CD8+ T Cells in Peripheral Blood and Tumor Tissue
时间窗: Patients were followed 22 days.
'Responders' will be defined as patients with at least a two-fold increase in the number of CD 8+ T cells (dextramer, ELISpot or both methods) in the peripheral blood and tissue at the final analysis.
次要结局
- Time to Progression (TTP)(The median follow up was 4.8 months (range 1.6 - 14.9 months).)
- Best Overall Response(The median follow up was 2.92 months (range 1.25 - 5.88months).)
- Median Progression-Free Survival(The median follow up was 4.8 months (range 1.6 - 14.9 months).)
- Median Overall Survival(The median follow up was 4.8 months (range 1.6 - 14.9 months).)
研究者
Kartik Sehgal, MD
Principal Investigator
Dana-Farber Cancer Institute