Vaccine + Chemotherapy for HPV-Related Throat Cancer

Overseen By Melissa L Wheatley

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inducers, CYP3A inhibitors, Glucocorticoids, Immunosuppressors

Disqualifiers: Neuropathy, Prior therapy, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat HPV-related throat cancer by combining the vaccine PRGN-2009 with standard chemotherapy drugs, cisplatin and docetaxel. The goal is to determine if this combination can extend patients' lives without the need for radiation, which often causes severe side effects. It targets individuals newly diagnosed with HPV-related throat cancer who plan to undergo surgery for removal. Participants will receive chemotherapy, and some will also receive the vaccine, followed by post-surgery care. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken certain investigational drugs, live vaccines, chemotherapy, or immunotherapy within 4 weeks before starting the trial, and you should not be on medications that affect liver enzymes (CYP3A) within 2 weeks before starting. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining cisplatin and docetaxel is generally well-tolerated, with manageable side effects for head and neck cancers. Common side effects include mouth sores and tiredness, but these are usually mild.

The vaccine PRGN-2009 remains under investigation, so less information is available about its safety compared to cisplatin and docetaxel. Researchers are studying whether it can safely improve treatment outcomes without the need for radiation.

Overall, the trial has reached a stage where researchers consider the treatment safe enough for more participants. However, since PRGN-2009 is not fully tested, discussing potential risks and benefits with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HPV-related throat cancer because they combine traditional chemotherapy with an innovative vaccine approach. Unlike standard treatments that rely solely on chemotherapy, Arm 2 introduces PRGN-2009, a therapeutic vaccine designed to stimulate the immune system to specifically target and attack HPV-related cancer cells. This dual approach not only aims to enhance the effectiveness of treatment but also potentially reduce side effects by targeting cancer more precisely. By integrating this novel vaccine with chemotherapy, there is hope for improved outcomes and a new avenue for treating this type of cancer.

What evidence suggests that this trial's treatments could be effective for HPV-related throat cancer?

Research has shown that using docetaxel and cisplatin together effectively treats throat cancer caused by HPV. Studies indicate that this combination works for 33% to 44% of head and neck cancer cases. As an initial treatment, it can lead to complete cancer disappearance in 89% of cases. Participants in this trial may receive this combination as part of Arm 1.

In Arm 2, participants will receive the same chemotherapy combination along with the PRGN-2009 vaccine. Early signs suggest the vaccine might enhance chemotherapy effectiveness. Designed to boost the immune system against HPV-related cancers, the vaccine holds promise. While more research is needed to confirm its additional benefits, there is hope it could improve survival rates without requiring radiation. ^{1 4 6 7 8}

Who Is on the Research Team?

Clint T Allen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed HPV-related throat cancer. Participants must pass a physical exam, blood tests, imaging scans, heart function and hearing tests. They should also provide a tumor tissue sample.

Inclusion Criteria

Participants must be willing to undergo pre-treatment PET/CT imaging study.

I have been tested positive for high-risk HPV.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

Positive beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening.

I do not have any unstable health conditions that could increase my risk.

I have had a transplant of tissue or an organ from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive neoadjuvant chemotherapy with docetaxel and cisplatin, with or without the PRGN-2009 vaccine, over three 3-week cycles

9 weeks

3 visits (in-person) for chemotherapy, 4 visits (in-person) for vaccine in Arm 2

Surgery

Participants undergo standard-of-care surgery to remove tumors 3 to 6 weeks after completing the study treatment

3-6 weeks post-treatment

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and recurrence-free survival at 3, 6, 12, and 24 months after surgery

24 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Docetaxel
• PRGN-2009

Trial Overview The study is testing the effectiveness of adding a vaccine (PRGN-2009) to standard chemotherapy drugs (Docetaxel and Cisplatin) in treating HPV-associated throat cancers without radiation. Half will receive the vaccine; all will undergo surgery post-treatment.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 3 Interventions

DCP (docetaxel + cisplatin + PRGN-2009)

Group II: Arm 1 Experimental Treatment 2 Interventions

DC (docetaxel + cisplatin)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 51 patients with HPV-related oropharyngeal squamous cell carcinoma, one course of TPF chemotherapy resulted in a high partial response rate of 73%, indicating its potential effectiveness in predicting outcomes for subsequent chemoradiotherapy.

The study found that 85% of patients who underwent chemoradiotherapy achieved a complete response, with a 2-year survival rate of 92%, suggesting that TPF can help guide treatment decisions between chemoradiotherapy and surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting the efficacy of chemoradiotherapy for locally advanced human papilloma virus-related oropharyngeal squamous cell carcinoma using one course of TPF chemotherapy. Kondo, T., Tsukahara, K., Okamoto, I., et al.[2021]

In a phase I study involving 20 patients with squamous cell carcinoma of the cervix, the combination of docetaxel and nedaplatin was found to be tolerable, with a maximum tolerated dose established at 70 mg/m2 for docetaxel and 100 mg/m2 for nedaplatin.

The treatment resulted in a partial response in 40% of patients, indicating potential efficacy even in those who had previously undergone cisplatin-based chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of docetaxel and nedaplatin for recurrent squamous cell carcinoma of the uterine cervix. Watanabe, Y., Nakai, H., Etoh, T., et al.[2018]

In a study of 143 patients with Stage III-IV head and neck squamous cell carcinoma, carboplatin-paclitaxel (CT) induction chemotherapy resulted in significantly better locoregional control (80.5%) and progression-free survival (73.2%) compared to docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy (55.5% and 60.7%, respectively).

TPF was associated with worse renal toxicity and a higher rate of chemotherapy dose reductions during treatment, suggesting that CT may be a safer and more effective option for patients undergoing induction chemotherapy before chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. Herman, LC., Chen, L., Garnett, A., et al.[2021]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

In a retrospective analysis of 119 patients from the EORTC 24971 trial, the addition of docetaxel to the PF regimen did not show a significant difference in treatment benefits based on HPV status, indicating that both HPV(+) and HPV(-) patients may benefit similarly from the TPF regimen.

The study found a low incidence of HPV positivity (14% for p16+ and 25% for HPV-DNA+) among the analyzed patients, suggesting that HPV status should not be used to determine treatment selection between TPF and PF in locoregionally advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study. Psyrri, A., Fortpied, C., Koutsodontis, G., et al.[2022]

In a phase III study involving 358 patients with advanced head and neck cancer, adding docetaxel to cisplatin and 5-fluorouracil (TPF) improved overall survival and reduced toxicity compared to the PF regimen.

Patients receiving TPF showed a trend towards better health-related quality of life (HRQOL) and experienced greater improvements in swallowing and coughing issues during treatment, suggesting that TPF may enhance patient well-being alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). van Herpen, CM., Mauer, ME., Mesia, R., et al.[2022]

In a phase II study involving 31 patients with advanced squamous cell carcinoma of the head and neck, docetaxel demonstrated significant activity, with a major response rate of 42% and a median response duration of 5 months.

Docetaxel was well tolerated, with manageable side effects such as leukopenia and fatigue, and the use of premedication helped reduce the incidence of severe toxicities, allowing for safe outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. Dreyfuss, AI., Clark, JR., Norris, CM., et al.[2018]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

The TP regimen (docetaxel combined with cisplatin) showed similar efficacy to the PF regimen (cisplatin combined with 5-fluorouracil) in treating nasopharyngeal carcinoma, with both regimens achieving high rates of complete remission after concurrent chemoradiotherapy.

However, the TP regimen was associated with significantly higher rates of severe neutropenia compared to the PF regimen, indicating a need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of efficacy of docetaxel combined cisplatin (TP regimen) and cisplatin combined 5-fluorouracil (PF regimen) on locally advanced nasopharyngeal carcinoma]. Xie, FY., Qi, SN., Hu, WH., et al.[2022]

Citations

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Efficacy and safety of cisplatin and weekly docetaxel in ... In the present study, the combination of cisplatin and weekly docetaxel chemotherapy as first-line treatment of R/M HNSCC showed high efficacy, with a 33.3% ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301614045325

Phase 2 Study of Docetaxel, Cisplatin, and Concurrent ... Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in ...

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Advances in the Management of HPV-Related ... Patients with human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than HPV-negative ...

4. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/484185

Rate of Pathologic Complete Responses to Docetaxel, ... Conclusions Induction chemotherapy with the TPF regimen results in a high pathological complete response rate (89%). This rate is higher than with the cisplatin ...

5. cancernetwork.com cancernetwork.com/view/role-docetaxel-management-squamous-cell-cancer-head-and-neck

The Role of Docetaxel in the Management of Squamous ... When combined with cisplatin, with or without fluorouracil (5-FU), in the treatment of recurrent disease, response rates of 33% to 44% have been observed for ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.TPS6117

Phase II trial of neoadjuvant chemotherapy (NAC) ... This trial will evaluate the rate of pCR with NAC (DC) alone or combined with PRGN-2009 (DCP) in pts with newly diagnosed HPV-OPC.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25832686/

Phase 2 study of docetaxel, cisplatin, and concurrent ... Conclusions: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa070956

Cisplatin and Fluorouracil Alone or with Docetaxel in Head ... A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin ...