Clinical trial NCT02865135: Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer of Head and Neck
Cancer of Cervix
Cancer of Anus
Keywords: HPV Related Head and Neck
Cervical
Anal Cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Stand Up To Cancer
First posted: 2016-08-12
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b]
timeFrame: Patients were followed for 50 days.
measure: Grade 1-2 Treatment-Related AE Rate
timeFrame: The median follow up was 2.92 months (range 1.25 - 5.88months).
measure: Changes in CD8+ T Cells in Peripheral Blood and Tumor Tissue
timeFrame: Patients were followed 22 days.
Secondary outcomes:
measure: Best Overall Response
timeFrame: The median follow up was 2.92 months (range 1.25 - 5.88months).
measure: Median Overall Survival
timeFrame: The median follow up was 4.8 months (range 1.6 - 14.9 months).
measure: Median Progression-Free Survival
timeFrame: The median follow up was 4.8 months (range 1.6 - 14.9 months).
measure: Time to Progression (TTP)
timeFrame: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute, Boston, MA02215
name: Kartik Seghal, MD
role: PRINCIPAL_INVESTIGATOR
References: