Biomarker-Guided Therapy for Oropharyngeal Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by David M, Routman, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Mayo Clinic

Must be taking: Cisplatin

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnancy, HIV, Active malignancy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial examines the use of blood-based biomarkers is to help inform decision making for treatment and radiation therapy for patients with human papillomavirus (HPV) positive oropharyngeal squamous cell cancers. The standard treatments for head and neck cancers are radiation therapy with chemotherapy or surgery potentially followed by radiation therapy with or without chemotherapy. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving chemotherapy along with radiation may kill more tumor cells. However, the cancer can recur or can spread to other parts of the body and all treatments can be associated with side effects. The purpose of this study is to evaluate a blood-based biomarker, using the NavDx testing device, for head and neck cancers in order to see if it can help improve selection of the intensity of treatment in order to best balance the side effects of treatment with the goal of decreasing cancer recurrence. This test could aid in early detection of recurrence and salvage therapy.

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 data supports the effectiveness of the treatment Blood-Based Biomarkers, NavDx testing device, ctHPV-DNA for oropharyngeal cancer?

Research shows that circulating tumor DNA (ctDNA) is a promising biomarker for monitoring treatment response and disease recurrence in HPV-related oropharyngeal cancer. Studies suggest that changes in ctDNA levels can help tailor treatment intensity, potentially improving outcomes and reducing side effects. ^{1 2 3 4 5}

Is the biomarker-guided therapy for oropharyngeal cancer safe for humans?

The research on circulating tumor DNA (ctDNA) as a biomarker for oropharyngeal cancer primarily focuses on its effectiveness in monitoring and diagnosing the disease, with no specific safety concerns mentioned in the studies. However, the trials aim to minimize treatment toxicity, suggesting a focus on safety in therapy approaches. ^{1 2 4 6 7}

How does the biomarker-guided treatment for oropharyngeal cancer differ from other treatments?

This treatment uses circulating tumor DNA (ctDNA) as a biomarker to guide therapy decisions, allowing for personalized treatment plans that can reduce unnecessary side effects by identifying patients who may benefit from less aggressive treatment. This approach is unique because it focuses on monitoring ctDNA levels to predict treatment response and detect disease recurrence, which is not commonly used in standard treatments for oropharyngeal cancer. ^{1 2 4 8 9}

Research Team

David M, Routman, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Blood-Based Biomarkers (Biomarker)

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.

Participant Groups

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+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The future of circulating tumor DNA as a biomarker in HPV related oropharyngeal squamous cell carcinoma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The Current Role of Human Papillomavirus Circulating Tumor DNA in Oropharynx Cancer. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Fluid Biomarkers in HPV and Non-HPV Related Oropharyngeal Carcinomas: From Diagnosis and Monitoring to Prognostication-A Systematic Review. [2022]

4. Switzerland 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. [2022]

5. England 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. [2022]

6. United States 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. [2023]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA in Human Papillomavirus-Mediated Oropharynx Cancer: Leveraging Early Data to Inform Future Directions. [2023]