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Vaccine Therapy and Cyclophosphamide in Treating Patients with HLA-A*02 Positive Relapsed, Refractory, or Metastatic HPV16-Related Oropharyngeal, Cervical, or Anal Cancer

Trial Status: Active

This phase Ib / II trial studies side effects and best dose of HPV16-E711-19 nanomer vaccine DPX-E7 and to see how well it works when given together with cyclophosphamide in treating patients with HLA-A*02 positive, human papillomavirus 16 (HPV16)-related oropharyngeal, cervical, or anal cancer that has come back, does not respond to treatment, or has spread to other parts of the body. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, 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. Giving HPV16-E711-19 nanomer vaccine DPX-E7 together with cyclophosphamide may work better in treating patients with HPV16-related oropharyngeal, cervical, or anal cancer.

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 the presence of HPV type16, detected by immunohistochemistry with P16 staining followed by polymerase chain reaction (PCR) 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); cervical cancer subjects with distant metastases will have received and failed bevacizumab prior to enrollment onto the trial
  • Accessible tumors for sequential biopsies
  • Recovery from toxicity from any prior therapy to National Cancer Institute Common 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)
  • Measurable disease, according to modified RECIST 1.1 and irRECIST
  • Eastern Cooperative Oncology Group performance status (ECOG PS) =< 2
  • Hemoglobin >= 10 g/dL
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Absolute lymphocyte count >= 400/uL
  • Platelet count >= 100,000/uL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X upper limit of normal (ULN)
  • Total bilirubin =< 1.5 X ULN
  • 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 vaccine
  • Chemotherapy or immunotherapy within 3 weeks prior to the first dose of vaccine
  • Prior malignancy 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 human immunodeficiency virus (HIV), or other condition that requires immunosuppressive therapy, including current use of high dose systemic corticosteroids
  • Autoimmune disease, such as systemic lupus erythematosus or rheumatoid arthritis, that is active and requires current immunosuppressive therapy
  • Active uncontrolled serious infection
  • WOCBP who have a positive beta-human chorionic gonadotropin (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

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Jochen Hanns-Martin Lorch
Phone: 617-632-3090

PRIMARY OBJECTIVES:

I. Evaluate changes in CD8+ T cells in peripheral blood and tumor tissue.

II. Evaluate the safety of HPV16-E711-19 nanomer vaccine DPX-E7 (DPX-E7) vaccination in HLA-A*02 positive patients with incurable HPV associated oropharyngeal cancer (HPVOC), cervical cancer, and anal cancer.

SECONDARY OBJECTIVES:

I. Evaluate the overall response rate (ORR) of DPX-E7 vaccination in HLA-A*02 positive patients with recurrent and/or metastatic HPVOC, cervical cancer, and anal cancer using modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related (ir)RECIST.

II. To estimate progression free survival, time to progression, and overall survival.

III. To evaluate the biologic correlates of response to therapy by determining the antigenspecific CD8 T cells elicited by E711-19 pMHC multimer binding assay, their activation status, effector/memory phenotype, cytokine profile, quantitation per ml blood, perforin/granzyme content, CD4 activation status, including regulatory T cell (Treg) profiling.

OUTLINE: This is a phase Ib, dose-escalation study of HPV16-E711-19 nanomer vaccine DPX-E7 followed by a phase II study.

Patients receive HPV16-E711-19 nanomer vaccine subcutaneously (SC) on days 1 and 22 and then every 8 weeks, and cyclophosphamide orally (PO) twice daily (BID) beginning 7 days before first vaccination, continuing for 7 days on and then 7 days off for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Jochen Hanns-Martin Lorch

  • Primary ID 15-578
  • Secondary IDs NCI-2016-02019
  • Clinicaltrials.gov ID NCT02865135