Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer

Study Overview
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Brief Summary
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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).

Detailed Description
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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

Official Title
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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

Conditions
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Cancer of Head and Neck, Cancer of Cervix, Cancer of Anus

Intervention / Treatment
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* Drug: DPX-E7 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DPX-E7 Vaccine<br>Subjects will 2 priming doses of DPX-E7 at a pre-determine dosage 3 weeks apart followed by a predetermine booster dose every 8 weeks until clinical progression. | Drug: DPX-E7 vaccine<br>* Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A*02 positive patients.<br>* Other names: HPV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events Related to Treatment |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | 2 years | 
| Overall Survival Rate |  | 2 years | 
| Progression Free Survival Rate |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV Related Head and Neck, Cervical, Anal Cancer