We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

TheraT® Vectors (Vaccines) Combined With Chemotherapy to Treat HPV16 Head and Neck Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05108870
Recruitment Status : Recruiting
First Posted : November 5, 2021
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Brief Summary:

Doctors leading this study hope to learn about the safety and effectiveness of combining medications HB-201 and HB-202 (also known as TheraT® vectors) with chemotherapy using carboplatin and paclitaxel in the beginning of the study (induction) and if combining these medications can increase tumor shrinkage after therapy and reduce the amount of radiotherapy and chemotherapy that will later be needed.

In addition, the study is looking at ways to reduce side effects overall using robotic surgery, chemotherapy and radiotherapy, or radiotherapy alone. Your participation in this research will last about 2 years.

HB-201 and HB-202 are experimental (meaning the US Food and Drug Administration (FDA) has not approved these drugs), and therefore they can only be given in a research study.


Condition or disease Intervention/treatment Phase
Human Papilloma Virus HPV HPV Positive Oropharyngeal Squamous Cell Carcinoma Head and Neck Cancer Drug: HB-201 Drug: HB-202 Drug: Carboplatin Drug: Paclitaxel Procedure: Transoral Robotic Surgery Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 4, 2022
Estimated Primary Completion Date : January 1, 2026
Estimated Study Completion Date : January 1, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1: Dose-Finding Group 1 - Drug Combination 1

All participants in this group will receive HB-201 combined with chemotherapy using carboplatin and paclitaxel.

- HB-201 will be administered on cycle 1 day 15, cycle 2 day 15, and cycle 3 day 15 with three 21-day cycles of carboplatin on day 1 and paclitaxel 100mg/m2 on days 1, 8, and 15

Drug: HB-201
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: HB-202
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: Carboplatin
Chemotherapy drug.

Drug: Paclitaxel
Chemotherapy drug.

Experimental: Phase 1: Dose-Finding Group 2 - Drug Combination 2

All participants in this group will receive alternating doses of HB-201 and HB-202 combined with chemotherapy using carboplatin and paclitaxel.

Participants will be given 3 doses of HB-201 & HB-202 alternating two vector therapy. Patients will receive 2 doses of HB-202 and 1 dose of HB-201. HB-202 will be administered on cycle 1 day 15 and cycle 3 day 15, and HB-201 will be administered on cycle 2 day 15 with three 21-day cycles of chemotherapy with carboplatin on day 1 and paclitaxel 100mg/m2 on days 1, 8, and 15.

Drug: HB-201
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: HB-202
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: Carboplatin
Chemotherapy drug.

Drug: Paclitaxel
Chemotherapy drug.

Experimental: Phase 2: Efficacy Arm 1 - HB-201 + Chemotherapy

Participants in this group will receive HB-201 combined with chemotherapy using carboplatin and paclitaxel at the dose established in the first phase of the study.

After completing treatment at the established phase 2 dose, subjects will receive surgery, radiotherapy alone, or chemotherapy with radiotherapy together based on how their tumor responds to the medications.

Drug: HB-201
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: HB-202
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: Carboplatin
Chemotherapy drug.

Drug: Paclitaxel
Chemotherapy drug.

Procedure: Transoral Robotic Surgery
Transoral robotic surgery is a procedure to remove mouth and throat cancers in which a surgeon uses a sophisticated, computer-enhanced system to guide the surgical tools.
Other Name: TORS

Experimental: Phase 2: Efficacy Arm 2 - HB-201 and HB-202 + Chemotherapy

Participants in this group will receive alternating doses of HB-201 and HB-202 combined with chemotherapy using carboplatin and paclitaxel at the dose established in the first phase of the study.

After completing treatment at the established phase 2 dose, subjects will receive surgery, radiotherapy alone, or chemotherapy with radiotherapy together based on how their tumor responds to the medications.

Drug: HB-201
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: HB-202
A anti-cancer vaccine that treats HPV-related cancers.
Other Name: TheraT® Vectors

Drug: Carboplatin
Chemotherapy drug.

Drug: Paclitaxel
Chemotherapy drug.

Procedure: Transoral Robotic Surgery
Transoral robotic surgery is a procedure to remove mouth and throat cancers in which a surgeon uses a sophisticated, computer-enhanced system to guide the surgical tools.
Other Name: TORS




Primary Outcome Measures :
  1. Phase 1 Primary Outcome: Phase 1 Dose of HB-201 and HB-201/202 Combined with Chemotherapy [ Time Frame: 2 years ]
    The phase 1 dose of HB-201 monotherapy and alternating HB-201 and 202 therapy in combination with chemotherapy in patients with HPV 16 head and neck cancer as assessed by data on reported dose-limiting toxicities (side effects) among participants. These side effects will be measures according to the Common Terminology Criteria for Adverse Events version 5

  2. Phase 2 Primary Outcome: Deep Response Rate of Participants Treated with HB-201 or HB-201/202 Combined with Chemotherapy [ Time Frame: 2 years ]
    The deep response rate (DRR) of participants who receive neoadjuvant HB-201 monotherapy combined with chemotherapy or alternating doses of HB-201 and HB-202 combined with chemotherapy. This response rate will be assessed by tumor shrinkage according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).


Secondary Outcome Measures :
  1. Correlation Between Plasma HPV-DNA and Tumor HPV-DNA [ Time Frame: 2 years ]
    Correlation between plasma HPV-DNA and tumor HPV-DNA as assessed by an analysis of plasma and sputum samples of participants using next generation sequencing analysis.

  2. Changes in Plasma HPV-DNA During Study Treatment with HB-201 and Alternating HB201/202 Combined with Chemotherapy [ Time Frame: 2 years ]
    Changes in the amount of HPV-DNA found in plasma during neoadjuvant HB-201 monotherapy and HB-201 and HB-202 alternating two-vector therapy combined with chemotherapy as assessed by next generation sequencing analysis of participants' plasma samples.

  3. Pathologic Response in Participants Undergoing Transoral Robotic Surgery (TORS) [ Time Frame: 2 years ]
    Pathologic response in patients undergoing TORS following neoadjuvant HB-201 monotherapy and HB-202 alternating two-vector therapy combined with chemotherapy. Response will be assessed by tumor shrinkage according to Response Evaluation Criteria in Solid Tumors 1.1.

  4. Progression Free Survival [ Time Frame: 2 years ]
    Progression-free survival of participants as assessed by data recorded in study/clinical records and statistical analysis.

  5. Overall Survival [ Time Frame: 2 years ]
    Overall survival of participants as assessed by data recorded in study/clinical records and statistical analysis.

  6. Locoregional Control [ Time Frame: 2 years ]
    Locoregional control of participants as assessed by data recorded in study/clinical records and statistical analysis.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05108870


Contacts
Layout table for location contacts
Contact: Clinical Trials Email 1-855-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Locations
Layout table for location information
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Clinical Trials Intake    855-702-8222    cancerclinicaltrials@bsd.uchicago.edu   
Principal Investigator: Ari Rosenberg, MD         
Sponsors and Collaborators
University of Chicago
Investigators
Layout table for investigator information
Principal Investigator: Ari Rosenberg, MD University of Chicago - Comprehensive Cancer Center
Layout table for additonal information
Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT05108870    
Other Study ID Numbers: IRB21-1031
First Posted: November 5, 2021    Key Record Dates
Last Update Posted: August 15, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Chicago:
throat cancer
human papilloma virus
HPV16
head and neck cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Head and Neck Neoplasms
Papilloma
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action