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

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

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).

Study Overview

• Status: Completed
• Conditions: Cancer of Head and Neck; Cancer of Cervix; Cancer of Anus
• Intervention / Treatment: Drug: DPX-E7 vaccine; Drug: Cyclophosphamide

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

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: DPX-E7 vaccine; Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A*02 positive patients.; Other Names: HPV vaccine; 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.; Other Names: Cytoxan
Experimental: 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.	Drug: DPX-E7 vaccine; Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A*02 positive patients.; Other Names: HPV vaccine; 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.; Other Names: Cytoxan
Experimental: 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.	Drug: DPX-E7 vaccine; Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A*02 positive patients.; Other Names: HPV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b]	A DLT was defined as any grade 3 or greater adverse event at least possibly related to the study agent including injection site reactions; or grade 2 or greater allergic reactions which occur in a subject prior to day 50, will trigger DLT. In addition, to be considered as DLT, the adverse event must be considered at least possibly related to study treatment. Grade 3 or greater abnormal lab values lasting <= 72 hours might be excluded as DLTs if there are no accompanying clinical signs and symptoms per investigator's discretion.	Patients were followed for 50 days.
Grade 1-2 Treatment-Related AE Rate	The proportion of participants who experienced grade 1-2 treatment-related adverse events based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) as reported on case report forms.	The median follow up was 2.92 months (range 1.25 - 5.88months).
Changes in CD8+ T Cells in Peripheral Blood and Tumor Tissue	'Responders' will be defined as patients with at least a two-fold increase in the number of CD 8+ T cells (dextramer, ELISpot or both methods) in the peripheral blood and tissue at the final analysis.	Patients were followed 22 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response	Best Overall Response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started) based on modified RECIST 1.1 and irRECIST. Per irRECIST, CR was defined as disappearance of all lesions in two consecutive observations not less than four weeks apart; PR was defined as greater than or equal to 50% decrease in tumor burden compared with baseline in two observations at least four weeks apart.	The median follow up was 2.92 months (range 1.25 - 5.88months).
Median Overall Survival	Overall survival based on the Kaplan-Meier method is defined as the time the start of treatment to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.	The median follow up was 4.8 months (range 1.6 - 14.9 months).
Median Progression-Free Survival	PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study or the appearance of one or more new lesions. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.	The median follow up was 4.8 months (range 1.6 - 14.9 months).
Time to Progression (TTP)	TTP is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study. Participants alive without PD were censored at the earliest of the date of the last disease evaluation. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study or the appearance of one or more new lesions. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.	The median follow up was 4.8 months (range 1.6 - 14.9 months).

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Stand Up To Cancer
• Investigators: Principal Investigator: Kartik Seghal, MD, Dana-Farber Cancer Institute, Boston, MA02215

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2017
• Primary Completion (Actual): October 4, 2019
• Study Completion (Actual): February 6, 2023

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimated): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cervical; Anal Cancer; HPV Related Head and Neck
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Head and Neck Neoplasms; Anus Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Vaccines
• Other Study ID Numbers: 15-578

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No