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.
...
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.
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.
Single group
Docetaxel
DrugDocetaxel 75 mg/m\^2 will be administered over 60 (+/-10) minutes.
Cisplatin
DrugCisplatin 75 mg/m\^2 will be administered over 120 (+/-10) minutes.
PRGN-2009
DrugPRGN-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.
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.
Determine the toxicity observed with DC and DCP
Safety will be evaluated by determining the frequency of adverse events among treated participants and reporting the results, by maximum grade of event and type of toxicity noted. Tolerability will be recorded in the form of number of participants that discontinued treatment, had a delay in any study treatment or a DC dose reduction, and any study drug-related surgical delays.
Determine 2-year recurrence-free survival (RFS) observed with DC and DCP
Recurrence-free survival will be determined using the Kaplan-Meier method for each arm, with recurrence or death without recurrence considered as events. The two-year recurrence-free survival values will be reported along with a 95% two-sided confidence interval for each arm. The two curves will also be compared using a two-tailed log-rank test.
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