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

NCT ID: NCT02865135

Last Updated: 2024-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2023-02-06

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

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

DPX-E7 vaccine

Intervention Type: DRUG

Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A\*02 positive patients.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide is a medication primarily used in the management and treatment of neoplasms, including multiple myeloma, sarcoma, and breast cancer. Cyclophosphamide is a nitrogen mustard that exerts its anti-neoplastic effects through alkylation.

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.

Group Type: EXPERIMENTAL

DPX-E7 vaccine

Intervention Type: DRUG

Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A\*02 positive patients.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide is a medication primarily used in the management and treatment of neoplasms, including multiple myeloma, sarcoma, and breast cancer. Cyclophosphamide is a nitrogen mustard that exerts its anti-neoplastic effects through alkylation.

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.

Group Type: EXPERIMENTAL

DPX-E7 vaccine

Intervention Type: DRUG

Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A\*02 positive patients.

Interventions

DPX-E7 vaccine

Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A\*02 positive patients.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide is a medication primarily used in the management and treatment of neoplasms, including multiple myeloma, sarcoma, and breast cancer. Cyclophosphamide is a nitrogen mustard that exerts its anti-neoplastic effects through alkylation.

Intervention Type: DRUG

Other Intervention Names

HPV vaccine; Cytoxan

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stand Up To Cancer

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Kartik Sehgal, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kartik Seghal, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute, Boston, MA02215

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15-578

Identifier Type: -

Identifier Source: org_study_id