Combining TheraT® Vaccines with Chemotherapy for HPV16 Head and Neck Cancers

A Randomized Phase I/II Trial of TheraT® Vectors Expressing HPV16 Specific Antigens in Combination With Neoadjuvant Chemotherapy Followed by Transoral Robotic Surgery or Risk/Response Stratified Chemoradiotherapy for Locoregional HPV16+ Oropharyngeal Cancer

This study is testing whether combining new vaccines with chemotherapy can help people with HPV16-positive head and neck cancers shrink their tumors more effectively and reduce the need for more treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Chicago (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT05108870 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and effectiveness of combining experimental medications HB-201 and HB-202 (TheraT® vectors) with chemotherapy agents carboplatin and paclitaxel for treating HPV16-positive head and neck cancers. The goal is to enhance tumor shrinkage during initial treatment and potentially reduce the need for subsequent chemotherapy and radiotherapy. Additionally, the study will explore methods to minimize side effects through various treatment approaches, including robotic surgery. Participation in this research will last approximately two years.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed HPV16-positive oropharyngeal squamous cell carcinoma.

Not a fit: Patients who have previously received radiation or chemotherapy for head and neck cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective treatment options with fewer side effects for patients with HPV16-positive head and neck cancers.

How similar studies have performed: While the combination of vaccines and chemotherapy is a novel approach, similar studies have shown promise in enhancing treatment outcomes for HPV-related cancers.

Eligibility criteria

INCLUSION CRITERIA

1. Subjects must have clinically confirmed human papilloma virus (HPV)16-positive head and neck squamous cell carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
2. Must have HPV16 subtype demonstrated based on clinical guidelines established by the study doctor.
3. Availability of ≥10 unstained 5 micron slides (to be provided to Human Tissue Resource Center at the University of Chicago). Participants who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
4. Participants must be at least 18 years of age.
5. Subjects with American Joint Committee on Cancer (8th edition, 2018) N1 (solitary lymph node \>=3cm), N2-N3 nodal disease or T3-T4 primary tumor (with any N).
6. Measurable disease (either primary site and/or nodal disease) by Response Evaluation Criteria in Solid Tumors 1.1.
7. No previous radiation or chemotherapy for a head and neck cancer.
8. No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual measurable disease is acceptable.) No surgical procedures or biopsies will occur after baseline scans are performed and measurable lesions are identified.
9. Eastern Cooperative Oncology Group performance status 0-1
10. Normal Organ Function as confirmed by clinical lab values.
11. Must be considered to be a candidate to receive cisplatin by the treating physician.
12. Must sign a study-specific informed consent form prior to study entry. Patients should have the ability to understand and the willingness to sign a written informed consent document.
13. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
14. Women must not be breastfeeding.
15. Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment.
16. Men who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s).

EXCLUSION CRITERIA

1. Unequivocal demonstration of distant metastatic disease (M1 disease).
2. Non-HPV16 subtype.
3. Unidentifiable primary site.
4. Intercurrent medical illnesses that impairs the patient's tolerance to therapy or limits survival. This includes but is not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Patients with clinically stable and/or chronically managed medical illnesses that are not symptomatic and/or are not expected to impact treatment on protocol are still eligible (conditions to be reviewed by the PI to confirm eligibility).
5. Active, known, or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy, with the exception of low-dose prednisone (\<= 10mg or equivalent). The following are exceptions to these criteria:

   * Patients with vitiligo or alopecia.
   * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
   * Any chronic skin condition that does not require systemic treatment.
6. Treatment with any chronic immunosuppressive medication within six months prior to the first administration of study treatment (unless agreed otherwise).
7. Participants who have had a prior anaphylactic or other severe reaction to human immunoglobulin or antibody formulation administration.
8. Herbal remedies with immune-stimulating properties or known to potentially interfere with major organ function within 28 days prior to the first dose of study treatment, unless agreed otherwise with the primary investigator.
9. Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment as discussed above.
10. Participants receiving other investigational agents.
11. Prior systemic anti-cancer treatment within the last 8 weeks.
12. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence life expectancy in the subsequent 3 years without active treatment.
13. Has known history of, or any evidence of active, non-infectious pneumonitis.
14. Has known active Hepatitis B or hepatitis C. If eradicated, patient is eligible.
15. Has received a live vaccine within 28 days of planned start of study therapy.

Where this trial is running

Chicago, Illinois

• University of Chicago — Chicago, Illinois, United States (Recruiting)

Study contacts

• Principal investigator: Ari Rosenberg, MD — University of Chicago - Comprehensive Cancer Center
• Study coordinator: Clinical Trials Email

Conditions Human Papilloma Virus; HPV; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Head and Neck Cancer; throat cancer; human papilloma virus; HPV16; head and neck cancer