Phase II Trial of Neoadjuvant Chemotherapy (NAC) Alone or in Combination With Immunotherapy Vaccine PRGN-2009 in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal (Head and Neck) Cancer

NCT06223568 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001730001730-C
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Throat cancer is a common tumor that can occur in people infected with the human papilloma virus (HPV). Most people with this cancer survive more than 5 years with standard chemotherapy drugs plus radiation. But radiation can cause serious adverse effects. Researchers believe that adding a vaccine (PRGN-2009) to this drug therapy may improve survival without the need for radiation. Objective: To test a study vaccine combined with standard chemotherapy in patients with HPV-associated throat cancers. Eligibility: People aged 18 years and older with newly diagnosed throat cancer associated with HPV. Design: Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and tests of their heart function and hearing. They will provide a sample of tissue from their tumor. A recent sample may be used; if none is available, a new sample will be taken. All participants will get two common drugs for treating cancer. These drugs are given through a tube attached to a needle inserted into a vein in the arm. Participants will receive these drugs on the first day of three 3-week cycles. Half of the participants will also get the vaccine. PRGN-2009 is injected under the skin in the arm. They will get these shots 4 times: 7 days before the start of the first cycle and on the 11th day of each cycle. Participants will have standard surgery to remove their tumors 3 to 6 weeks after completing the study treatment. They will have follow-up visits 3, 6, 12, and 24 months after their surgery. ...

Conditions

Squamous Cell Carcinoma of the Head and Neck; Drug Therapy; Cancer Vaccine; Oropharynx; Human Papillomavirus Viruses

Keywords

Neoadjuvant Chemotherapy; Oropharynx Cancer; Human Papillomavirus; Therapeutic Vaccine

Outcome Measures

Primary Outcomes (1)

• Determine the rate of pCR with NAC (DC) alone or in combination with PRGN-2009 (DCP) in participants with newly diagnosed HPV-associated OPSCC

  The pCR rates will be determined on each arm and will be reported along with a 95% confidence interval. The two rates will be compared using a one-sided Fisher s exact test.

  6 months

Secondary Outcomes (2)

• Determine the toxicity observed with DC and DCP

  Day 1 (all arms) and day 11 (Arm 2 only) of every cycle and Day -7 of C1 (Arm 2 only), and at Safety Follow-Up visit which occurs 14 (+14) days after the study agent (s) was/were last administered. 3-month follow-up visit and beyond.

• Determine 2-year recurrence-free survival (RFS) observed with DC and DCP

  3, 6, 12, 24 months after surgery per SOC until recurrence.

Study Arms (2)

Arm 1

EXPERIMENTAL

DC (docetaxel + cisplatin)

Drug: Docetaxel; Drug: Cisplatin

Arm 2

EXPERIMENTAL

DCP (docetaxel + cisplatin + PRGN-2009)

Drug: Docetaxel; Drug: Cisplatin; Drug: PRGN-2009

Interventions

Docetaxel DRUG

Docetaxel 75 mg/m\^2 will be administered over 60 (+/-10) minutes.

Arm 1; Arm 2

Cisplatin DRUG

Cisplatin 75 mg/m\^2 will be administered over 120 (+/-10) minutes.

Arm 1; Arm 2

PRGN-2009 DRUG

PRGN-2009 will be administered in Arm 2 participants only as an SQ injection in the arm at a dose of 1 mL nominally containing 5x10\^11 viral particles (VP) on Day -7 (+/-3 days) of Cycle 1, Day 11 (+/-3 days) of Cycles 1, 2, and 3.

Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed surgically resectable newly diagnosed stage I (cT1-2, N0-1) or II (T1-3, N0-2), M0 oropharyngeal squamous cell carcinoma. Note: Pathological report of cancer diagnosis may be from the primary tumor or from a metastatic cervical lymph node.
• History of HPV-positive status determined by a standard-of-care HPV testing. Note: All participants with high-risk HPV serotypes are eligible.
• Age \>= 18 years.
• ECOG performance status \<= 2.
• Individuals who smoke currently must smoke \<10 pack years. Note: Former smokers with any pack-year history are eligible if quit smoking \>10 years before study treatment initiation. Former smokers who quit \<10 years before study treatment initiation must have smoked \<10 pack years.
• Planned for cancer removal surgery per standard of care (SOC) and individual had agreed for the cancer removal surgery.
• Individuals must have adequate organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9.0 g/dL
• Platelet count \>= 100 x 10\^9/L
• Creatinine \<= 1.2 x upper limit of normal (ULN) OR calculated creatinine clearance \>=55 mL/min/1.73m\^2 by Cockcroft-Gault formula
• Total bilirubin \<= 1 x ULN, or \<= 3 x ULN in patients with known or suspected Gilbert's Syndrome
• Alanine aminotransferase (ALT) \<= 1.5 x ULN
• Aspartate aminotransferase (AST) \<= 1.5 x ULN
• Individuals serologically positive for human immunodeficiency virus (HIV) must:

You may not qualify if:

• Peripheral motor or sensory neuropathy \> Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v.5 at screening.
• Prior therapy with an investigational drug, live vaccine, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone-directed therapy) within 4 weeks prior to the first study drug administration. Note: Participants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast).
• Prior therapy with any medications or substances that are moderate or strong inducers or moderate or strong inhibitors of cytochrome P450 (CYP3A) https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#table2-2,table3-3,table5-2 within 2 weeks prior to the first study drug administration.
• History of allergic reactions attributed to compounds of similar chemical or biological composition to drugs used in the study.
• Systemic (intravenous or oral) glucocorticoid (except for physiologic doses of corticosteroids, i.e., \<= the equivalent of prednisone 10 mg/day) or other immunosuppressors such as azathioprine or cyclosporin A within 1 week prior to study treatment initiation. Note: Glucocorticoids as premedication for contrast-enhanced studies are allowed.
• Second malignancy active within the previous 2 years except for indolent or locally curable malignancy that is currently considered cured and/or does not require an additional standard of care treatment, such as, but not limited to, cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer or differentiated thyroid cancer.
• Prior allogenic tissue/solid organ transplant.
• History of heart failure.
• Positive beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening.
• Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history and physical exam or situations that are not stable (e.g., recent hospitalization, Emergency Room visit or undergoing medication changes) that would potentially increase risk for the participant.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms

Interventions

Docetaxel; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Clint T Allen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa L Wheatley

CONTACT

(240) 858-3391; melissa.wheatley@nih.gov

Clint T Allen, M.D.

CONTACT

(301) 402-4216; clint.allen@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: January 25, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): January 10, 2028
• Study Completion (Estimated): January 10, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)