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

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cancer of Anus; Cancer of Head and Neck; Cancer of Cervix

Treatments: Drug: DPX-E7 vaccine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02865135

15-578

Details and patient eligibility

About

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).

Full 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

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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11 participants in 3 patient groups

DPX-E7 + Cyclophosphamide [Phase Ib Cohort]

Experimental group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Drug: DPX-E7 vaccine

DPX-E7 + Cyclophosphamide [Phase II Cohort 1]

Experimental group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Drug: DPX-E7 vaccine

DPX-E7 [Phase II Cohort 2]

Experimental group

Description:

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.

Treatment:

Drug: DPX-E7 vaccine