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

NCT02865135 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 15-578
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

HPV Related Head and Neck; Cervical; Anal Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Best Overall Response

  The median follow up was 2.92 months (range 1.25 - 5.88months).

• Median Overall Survival

  The median follow up was 4.8 months (range 1.6 - 14.9 months).

• Median Progression-Free Survival

  The median follow up was 4.8 months (range 1.6 - 14.9 months).

• Time to Progression (TTP)

  The median follow up was 4.8 months (range 1.6 - 14.9 months).

Study Arms (3)

DPX-E7 + Cyclophosphamide [Phase Ib Cohort]

EXPERIMENTAL

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; Drug: Cyclophosphamide

DPX-E7 + Cyclophosphamide [Phase II Cohort 1]

EXPERIMENTAL

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; Drug: Cyclophosphamide

DPX-E7 [Phase II Cohort 2]

EXPERIMENTAL

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

Interventions

DPX-E7 vaccine DRUG

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

Also known as: HPV vaccine

DPX-E7 + Cyclophosphamide [Phase II Cohort 1]; DPX-E7 + Cyclophosphamide [Phase Ib Cohort]; DPX-E7 [Phase II Cohort 2]

Cyclophosphamide 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.

Also known as: Cytoxan

DPX-E7 + Cyclophosphamide [Phase II Cohort 1]; DPX-E7 + Cyclophosphamide [Phase Ib Cohort]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Stand Up To Cancer: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Uterine Cervical Neoplasms; Anus Neoplasms

Interventions

Papillomavirus Vaccines; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Week accrual leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Kartik Sehgal, MD
• Organization: Dana Farber Cancer Institute (DFCI)

Kartik_Sehgal@dfci.harvard.edu

617-632-3090

Study Officials

• Kartik Seghal, MD

  Dana-Farber Cancer Institute, Boston, MA02215

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: August 12, 2016
• Study Start: March 30, 2017
• Primary Completion: October 4, 2019
• Study Completion: February 6, 2023
• Last Updated: January 11, 2024
• Results First Posted: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)