Biomarker-Guided Therapy for Oropharyngeal Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Cisplatin

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnancy, HIV, Active malignancy, 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: 3

Duration: 6-8 weeks

455 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a blood test can tailor treatments for individuals with HPV-positive oropharyngeal cancer, a type of throat cancer caused by the human papillomavirus. The goal is to determine if this test can guide treatment intensity, balancing effectiveness with fewer side effects. The trial includes various treatment paths, such as combinations of surgery, chemotherapy, and radiation, based on biomarker results. Individuals diagnosed with HPV-positive throat cancer and planning standard cancer treatments might be suitable for this study. As a Phase 2 trial, the research focuses on measuring treatment effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in personalized 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, if you are taking medications that might interfere with the treatment, the investigators may ask you to stop them.

What prior data suggests that the NavDx testing device is safe for use in patients with oropharyngeal cancer?

A previous study found that DART therapy with docetaxel was well-tolerated in patients with throat cancer. The survival rate was high, and patients experienced fewer side effects compared to traditional treatments, suggesting it is relatively safe for human use.

For advanced radiation therapy (IMRT/IMPT) with or without cisplatin, studies have shown fewer long-term side effects than expected. The treatments effectively controlled the cancer, indicating a good safety profile for patients.

These findings demonstrate that both treatment approaches are generally safe and manageable, though individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of blood-based biomarkers for guiding therapy in oropharyngeal cancer because it offers a personalized approach to treatment. Unlike standard treatments like surgery, radiation, and chemotherapy alone, this method can help tailor the intensity and type of treatment based on individual biomarker responses. This approach potentially minimizes unnecessary exposure to harsh treatments, reducing side effects and improving patient outcomes. By closely monitoring biomarkers, doctors can adapt treatment plans more dynamically, aiming for more effective cancer control.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Research has shown that blood tests, such as the NavDx device, can help customize treatment for HPV-positive throat cancer. In this trial, participants in Group 2 will receive a gentler form of radiation therapy (DART) combined with the drug docetaxel. Studies found that 96.2% of patients had their tumors well-controlled in the treated area, and 91.1% did not experience cancer progression. Participants in Groups 3 and 4 will receive advanced radiation therapies, such as IMRT and IMPT, with or without the drug cisplatin. These treatments have effectively controlled cancer, maintained high survival rates, and may reduce side effects. The goal is to lower the chance of cancer recurrence while effectively managing side effects. ^{4 5 6 7 8}

Who Is on the Research Team?

David M, Routman, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with HPV-positive oropharyngeal squamous cell cancers eligible for surgery or chemoradiotherapy can join. They must not have distant metastases, be HIV+ or immunocompromised, and women of childbearing potential need a recent negative pregnancy test. Participants should be able to complete questionnaires and provide blood samples.

Inclusion Criteria

I am fully active or can carry out light work.

PRE-REGISTRATION: Provide written informed consent

Willing to provide blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx testing

Exclusion Criteria

Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)+

Pregnant women

I will receive all my cancer treatments, including surgery and chemotherapy, at the hospital conducting the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo various treatment regimens including DART, IMRT, or IMPT with or without chemotherapy based on group assignment

6-8 weeks

Daily visits for radiation therapy, weekly or bi-weekly for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with imaging and biomarker testing at regular intervals

5 years

Every 3 months for 2 years, then every 6 months for year 3, and annually for years 4 and 5

Observation

Participants in Group 1 undergo observation following standard of care surgery

3 months

Regular imaging and biomarker testing

What Are the Treatments Tested in This Trial?

Interventions

• Blood-Based Biomarkers

Trial Overview The trial is testing if blood-based biomarkers can guide treatment intensity for better outcomes in head and neck cancer patients. It involves standard treatments like radiation (using high energy rays) and chemotherapy (with drugs like cisplatin), along with new tests using the NavDx device to detect cancer recurrence early.

How Is the Trial Designed?

Group I: Group 4 (IMRT/IMPT, cisplatin) Experimental Treatment 9 Interventions

Patients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

Group II: Group 3 (IMRT/IMPT, with/without cisplatin) Experimental Treatment 10 Interventions

Patients undergo IMRT or IMPT QD on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

Group III: Group 2 (DART, docetaxel) Experimental Treatment 9 Interventions

Patients undergo DART with/without mucosal sparing BID on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel IV over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

Group IV: Group 1 (observation) Active Control 8 Interventions

Patients undergo observation following standard of care surgery. Patients undergo modified barium swallow study (MBSS) at pre-op, 2 weeks post-op, and 3 months follow-up. Patients also undergo CT, PET/CT, or magnetic MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

HPV-related oropharyngeal squamous cell carcinoma (OPSCC) generally has better treatment outcomes compared to non-virally mediated cancers, prompting research into strategies that reduce treatment toxicity while maintaining survival rates.

Circulating tumor (ct) DNA is a promising biomarker for monitoring treatment response and disease recurrence in head and neck cancers, particularly in HPV-related OPSCC, suggesting potential for its integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of circulating tumor DNA as a biomarker in HPV related oropharyngeal squamous cell carcinoma. Haring, CT., Dermody, SM., Yalamanchi, P., et al.[2022]

Circulating tumor DNA (ctDNA) is a promising biomarker for diagnosing and monitoring human papillomavirus-related oropharyngeal squamous cell carcinoma, potentially improving patient management.

Changes in ctDNA levels during and after treatment may indicate disease response, which could inform decisions on whether to intensify or reduce treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Role of Human Papillomavirus Circulating Tumor DNA in Oropharynx Cancer. Regan, SN., Mierzwa, ML.[2023]

The study proposes a new clinical trial to use circulating tumor DNA (cfHPVDNA) levels to identify patients with HPV-associated oropharyngeal squamous cell carcinoma who may safely undergo de-escalated therapy, potentially reducing long-term treatment toxicity.

Patients with undetectable cfHPVDNA after surgery will be categorized into low-risk or high-risk groups, with low-risk patients possibly receiving observation instead of radiation, while high-risk patients will continue with standard adjuvant therapy, aiming to evaluate disease recurrence and survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Sinai Robotic Surgery Trial in HPV-related oropharyngeal squamous cell carcinoma (SIRS 2.0 trial) - study protocol for a phase II non-randomized non-inferiority trial. Chai, RL., Ferrandino, RM., Barron, C., et al.[2022]

Circulating tumor DNA (ctDNA) is a promising biomarker in oropharyngeal squamous cell carcinoma, particularly for patients with human papillomavirus (HPV)-related cancers, as it may help in assessing prognosis and monitoring treatment response.

Current research highlights the importance of understanding ctDNA dynamics, especially in clinical trials aimed at treatment de-escalation, indicating its potential role in detecting minimal residual disease and guiding future therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA in Human Papillomavirus-Mediated Oropharynx Cancer: Leveraging Early Data to Inform Future Directions. Heft Neal, ME., Walline, HM., Haring, CT.[2023]

A meta-analysis of 13 studies involving 998 patients showed that circulating tumor HPV DNA (ctHPVDNA) detected by ddPCR has high sensitivity (90%) and specificity (94%) for diagnosing HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).

The results suggest that ctHPVDNA monitoring could enhance the diagnostic and therapeutic management of cancer patients, providing valuable insights into tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: Systematic review and meta-analysis. Paolini, F., Campo, F., Iocca, O., et al.[2023]

The novel TTMV-HPV-DNA assay for detecting recurrences in HPV-driven oropharynx cancer is potentially more cost-effective than traditional surveillance methods, despite higher initial costs, with cumulative costs of $20,756 for TTMV-HPV-DNA compared to $11,674 for standard methods over 5 years.

The TTMV-HPV-DNA strategy could become cost-saving if it leads to reduced imaging use and small improvements in patient quality or quantity of life, suggesting it may enhance post-treatment surveillance efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The economic impact of circulating tumor-tissue modified HPV DNA for the post-treatment surveillance of HPV-driven oropharyngeal cancer: A simulation. Ward, MC., Miller, JA., Walker, GV., et al.[2022]

This study highlights the potential of using quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma as a non-invasive biomarker to assess treatment response and guide personalized therapy for patients with HPV-associated oropharyngeal cancer (OPC).

The research indicates that response to induction chemotherapy can predict which patients may benefit from de-escalated treatment strategies, aiming to reduce toxicity while maintaining effective outcomes, thus improving the overall management of HPV+ OPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment. Rosenberg, AJ., Izumchenko, E., Pearson, A., et al.[2022]

In a study of 115 patients with HPV-associated oropharyngeal cancer, monitoring plasma circulating tumor HPV DNA (ctHPVDNA) during post-treatment surveillance showed a 100% negative predictive value (NPV), meaning that patients with undetectable ctHPVDNA did not experience disease recurrence.

The presence of ctHPVDNA in two consecutive blood tests had a positive predictive value (PPV) of 94%, indicating that this method can effectively identify patients at high risk for recurrence, potentially allowing for earlier treatment interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. Chera, BS., Kumar, S., Shen, C., et al.[2023]

A systematic review of 38 clinical trials identified promising non-invasive biomarkers in biofluids for detecting and monitoring oropharyngeal cancers (OPCs), which could enhance personalized medicine and reduce the need for invasive tissue biopsies.

These biomarkers, particularly in relation to HPV-status, show potential for improving detection, staging, and prognosis prediction, but further research is necessary to integrate them with existing diagnostic methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluid Biomarkers in HPV and Non-HPV Related Oropharyngeal Carcinomas: From Diagnosis and Monitoring to Prognostication-A Systematic Review. Lee, SC., Leung, KKC., Chung, ACY., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7336074/

Analyzing oropharyngeal cancer survival outcomes The median dose was 65 Gy delivered in 30 fractions, with a median overall treatment time of 39 days. Overall, 231 patients (84.6%) received systemic therapy.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02908477

Study Details | NCT02908477 | Evaluation of De-escalated ... Grade 3+ Adverse Events Rate, To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.

3. cancernetwork.com cancernetwork.com/view/dart-therapy-exhibits-greater-tolerability-in-oropharyngeal-scc

DART Therapy Exhibits Greater Tolerability in ... The 2-year overall survival rate in the DART and standard of care groups were 96.9% vs 98.3% with an HR of 1.68. Patients treated with de- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7098832/

Phase II Evaluation of Aggressive Dose De-Escalation for ... The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01932697

NCT01932697 | Radiation Therapy and Docetaxel in ... This phase II trial studies how well radiation therapy and docetaxel work in treating patients with human papillomavirus (HPV)-related oropharyngeal cancer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40402484/

A Secondary Analysis of the DART Phase 3 Randomized ... Interventions: The DART group received 30 to 36 Gy of radiation therapy in 1.5 to 1.8 Gy twice daily, plus docetaxel, 15 mg/m2, on days 1 and 8.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02908477

Study Details | NCT02908477 | Evaluation of De-escalated ... This study investigates a less intense radiation treatment following surgery that uses half the dose of radiation given over two weeks rather than six weeks.

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00324-9/abstract

De-escalated adjuvant radiotherapy versus standard ... The primary endpoint was cumulative, chronic grade 3 or higher toxicity rate 3–24 months after radiotherapy. Primary analysis was done in patients who received ...