Personalized De-escalation Treatment for Oropharyngeal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Paclitaxel, Carboplatin

Disqualifiers: Prior invasive malignancy, Severe co-morbidity, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat early-stage p16+ oropharyngeal cancer, which affects the throat area. Researchers are testing two treatment plans: one involves surgery followed by careful monitoring or additional treatment like radiation, and the other uses a tailored combination of chemotherapy and radiation (chemoradiation). The goal is to determine which approach is more effective and has fewer side effects. Individuals with stage I-II p16+ throat cancer who haven't received prior treatment for this cancer may be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have poorly controlled diabetes, adjustments to your medications might be necessary. It's best to discuss your specific situation with the trial team.

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

Research shows that combining chemotherapy and radiation (chemoradiation) for oropharyngeal cancer is generally safe and well-tolerated. Studies have found that this approach can lead to excellent survival rates for early-stage cancer, with a low risk of serious side effects. For instance, patients who received chemoradiation as their main treatment rarely needed long-term support like a feeding tube.

Surgery followed by additional treatments like radiation or chemoradiation is also considered safe. Research suggests that using only radiation, even at lower doses, effectively treats the cancer without increasing the risk of serious side effects.

In summary, both chemoradiation and surgical treatments for oropharyngeal cancer have proven safe, and patients generally handle these treatments well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for oropharyngeal cancer because they offer a personalized approach to de-escalation, unlike the traditional one-size-fits-all methods. The surgery arm tailors follow-up care based on individual risk, possibly involving less aggressive treatments like observation or more intensive ones like radiation or chemoradiation. The chemoradiation arm, on the other hand, adjusts the intensity of treatment based on risk assessment, potentially reducing unnecessary side effects while maintaining effectiveness. This individualized strategy aims to balance treatment effectiveness with quality of life, which is a significant improvement over current standard treatments.

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

Research has shown that combining chemotherapy and radiation, which participants in the "Definitive CRT" arm of this trial may receive, is a strong option for treating HPV-positive oropharyngeal cancer. Studies indicate that this standard treatment is highly effective, with 98% of patients not experiencing a return of cancer within two years. One study found that this combined treatment can be as effective as surgery for this type of cancer and usually results in fewer severe side effects, such as the need for a feeding tube. Meanwhile, the "Surgery" arm in this trial aims to reduce treatment intensity while maintaining good results, offering risk-adjusted adjuvant treatment options like observation, radiation, or chemoradiation. ^{2 3 6 7 8}

Who Is on the Research Team?

Michelle Mierzwa, M.D.

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage p16+ or HPV-positive squamous cell carcinoma of the oropharynx, who haven't had prior treatment for this cancer. They must have good bone marrow function and organ performance, no distant metastases, and be able to undergo PET/CT scans. Women and men must use birth control during the study.

Inclusion Criteria

My kidney function, measured by creatinine levels, is normal or nearly normal.

History/physical examination, including documentation of weight within 4 weeks prior to registration

I agree to use effective birth control during the study.

Exclusion Criteria

Active enrollment on another clinical trial involving active treatment for the study cancer

Severe, active co-morbidity

I have received treatment for my cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Observation/Risk-adjusted Adjuvant Treatment

Participants undergo surgery followed by observation or risk-adjusted adjuvant radiation (+/- chemo)

6-8 weeks

Definitive Chemoradiation (CRT)

Participants receive individualized adaptive definitive chemoradiation

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Chemoradiation
• Observation
• Post-operative radiation
• Surgery

Trial Overview The CuSToMIze trial at University of Michigan tests two less intense treatments for Stage I-II p16+ oropharyngeal cancer: (1) surgery followed by observation or adjusted radiation (+/- chemo), (2) personalized adaptive chemoradiation based on individual response.

How Is the Trial Designed?

Group I: Definitive CRT Experimental Treatment 1 Intervention

Risk-adjusted definitive chemoradiation.

Group II: Surgery Active Control 4 Interventions

Surgery followed by risk-adjusted adjuvant treatment (observation, radiation, or chemoradiation).

Chemoradiation is already approved in China for the following indications:

Approved in China as Baizean for:

• Classical Hodgkin’s lymphoma (cHL)
• Locally advanced or metastatic urothelial carcinoma (UC)
• Locally advanced or metastatic non-small cell lung cancer (NSCLC)
• Advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
• Locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
• Recurrent or metastatic nasopharyngeal cancer (NPC)

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Published Research Related to This Trial

Adjuvant intensity-modulated radiotherapy (IMRT) with or without chemotherapy (AT) significantly improved disease-free survival and local-regional control in HPV-positive oropharyngeal squamous cell carcinoma patients compared to definitive surgical therapy (ST), particularly in patients with tumors exhibiting extracapsular extension.

However, the AT approach was associated with higher toxicity rates, including dysphagia and mandibular osteonecrosis, with 19.0% of AT patients experiencing these issues compared to only 2.4% in the ST group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnitude of benefit for adjuvant radiotherapy following minimally invasive surgery in intermediate to high risk HPV-positive oropharyngeal squamous cell carcinoma. Pasalic, D., Funk, RK., García, JJ., et al.[2019]

In a study of 96 patients with locally advanced HPV-positive oropharyngeal cancer, both transoral robotic surgery (TORS) and intensity-modulated radiotherapy (IMRT) showed excellent survival rates, with overall survival at 97% for TORS and 98% for IMRT.

There were no significant differences in survival outcomes or treatment-related toxicities between the two treatment groups, suggesting that both approaches are effective and safe, but there is a need to refine treatments to minimize side effects while maintaining effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront transoral robotic surgery (TORS) versus intensity-modulated radiation therapy (IMRT) in HPV-positive oropharyngeal cancer: real-world data from a tertiary comprehensive cancer centre. Zorzi, SF., Agostini, G., Chu, F., et al.[2022]

In a study of 899 oropharyngeal cancer patients, those with HPV-positive tumors showed significantly better local and regional control rates compared to HPV-negative patients, indicating that HPV status is a crucial factor in treatment outcomes.

HPV-positive patients classified as low-risk (T1-3N0-2c) have a low risk of distant metastasis, but those with N2c status may not benefit from treatment deintensification strategies that exclude chemotherapy, as they showed lower distant control rates when treated with radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. O'Sullivan, B., Huang, SH., Siu, LL., et al.[2022]

In a study comparing 26 patients receiving radiotherapy with cetuximab (cet-RT) to 27 patients receiving chemotherapy (chemo-RT) for HPV+ oropharyngeal cancer, both groups showed similar functional outcomes and quality of life over time, despite some initial worsening in swallowing and quality of life scores.

The results suggest that using cetuximab instead of chemotherapy for treatment de-intensification in HPV+ oropharyngeal cancer may not provide significant advantages, as both treatment approaches yielded excellent clinical outcomes without notable differences in patient functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons of dysphagia and quality of life (QOL) in comparable patients with HPV-positive oropharyngeal cancer receiving chemo-irradiation or cetuximab-irradiation. Samuels, SE., Tao, Y., Lyden, T., et al.[2018]

Recent randomized trials indicate that omitting or substituting cisplatin in the treatment of HPV-positive oropharyngeal cancer leads to worse survival outcomes, highlighting the risks of treatment de-escalation.

The Head and Neck Cancer International Group recommends that any de-escalation strategies should first be tested in phase II studies before moving to larger phase III trials, emphasizing the need for high-level evidence to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-Escalation After DE-ESCALATE and RTOG 1016: A Head and Neck Cancer InterGroup Framework for Future De-Escalation Studies. Mehanna, H., Rischin, D., Wong, SJ., et al.[2021]

In a phase II clinical trial involving 114 patients with HPV-associated oropharyngeal cancer, a de-intensified treatment regimen of 60 Gy radiotherapy and low-dose cisplatin resulted in excellent 2-year outcomes: 95% local-regional control and 86% progression-free survival.

The study found that this treatment approach minimized the need for chemotherapy and surgery, with no severe late adverse events reported, indicating a safer and effective option for patients with minimal smoking history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Chera, BS., Amdur, RJ., Green, R., et al.[2021]

A systematic review of 10 prospective studies on therapy de-escalation for HPV-associated oropharyngeal cancer (OPC) suggests that reduced-dose chemoradiotherapy, especially when combined with induction chemotherapy, can achieve high 2-year progression-free survival (PFS) rates of 89% and overall survival (OS) rates of 96%.

While de-escalation strategies show promising efficacy, they also present some acute toxicities, with grade 3+ dysphagia and mucositis occurring in 9-39% of patients, indicating a need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. Patel, RR., Ludmir, EB., Augustyn, A., et al.[2021]

HPV-positive oropharyngeal cancer patients generally have a better prognosis and lower mortality rates compared to HPV-negative patients, leading to a reconsideration of treatment approaches.

Recent trials have explored de-intensification strategies for treating HPV-positive oropharyngeal cancer, aiming to reduce the side effects of standard chemo-radiotherapy without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-intensification for HPV positive oropharyngeal cancer: and yet it moves!: 2019 in review. Bonomo, P., Livi, L.[2020]

Patients with HPV+ oropharyngeal squamous cell carcinoma show significantly improved overall survival and disease-specific survival when treated with platinum-based chemotherapy combined with radiotherapy, as indicated by a meta-analysis of 1130 patients from nine ongoing randomized controlled trials.

One trial suggests that using the EGFR inhibitor cetuximab may lead to reduced survival outcomes in HPV+ patients, highlighting the need for careful consideration of treatment protocols in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials. Masterson, L., Moualed, D., Liu, ZW., et al.[2023]

HPV-related oropharyngeal cancers are on the rise in Western countries, prompting a need for tailored management strategies due to their unique cancer development and better prognosis compared to other cancers.

Recent clinical trials are exploring therapeutic de-escalation for these patients, suggesting that less aggressive treatment may be effective given their distinct oncogenesis and favorable outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Challenges and limits of therapeutic de-escalation for papillomavirus-related oropharyngeal cancer]. Modesto, A., Graff Cailleaud, P., Blanchard, P., et al.[2022]

A new tool was developed to standardize how treatment toxicity from chemoradiation therapy for oropharyngeal carcinoma is represented, helping doctors and patients make informed decisions about treatment options.

In a survey of 105 oncologists, mucositis and nausea were identified as the most distressing short-term toxicities, while pain and xerostomia were noted as the most concerning long-term effects, highlighting the importance of both short-term and long-term outcomes in treatment discussions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a chemoradiation therapy toxicity staging system for oropharyngeal carcinoma. Goepfert, RP., Yom, SS., Ryan, WR., et al.[2015]

In a study of 233 patients with advanced oropharyngeal squamous cell carcinoma, there was no significant difference in recurrence-free survival rates between those treated with primary surgery and those treated with radiotherapy, with rates of 76.3% and 84.9% at five years, respectively.

The primary pattern of failure for both treatment groups was distant metastatic disease, suggesting that while local failures occurred, they may be preventable through improved targeting in treatment planning, particularly near critical areas like the base of the skull.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy. Debenham, BJ., Banerjee, R., Warkentin, H., et al.[2020]

Citations

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

Analyzing oropharyngeal cancer survival outcomes Overall, 231 patients (84.6%) received systemic therapy. Cisplatin-based chemotherapy was administered to 209 patients (90.5%), whereas 22 patients (9.5%) ...

2. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2024/astro24yom

Existing standard chemoradiation superior to ... Randomized trial halted after two deintensification strategies failed to match standard of care's 98% rate of two-year progression-free survival.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2780537

Association of Advanced-Stage Oropharyngeal Squamous ... This study found that definitive chemoradiotherapy was associated with effectiveness that was comparable with that of upfront surgical treatment.

4. ascopost.com ascopost.com/issues/april-25-2025/study-finds-standard-chemoradiation-therapy-superior-to-deintensification-approaches-for-hpv-related-oropharyngeal-cancer/

Study Finds Standard Chemoradiation Therapy Superior to ... Current standard chemoradiation therapy remains the most effective treatment for selected patients with human papillomavirus (HPV)-positive oropharyngeal ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7654053/

Modern treatment outcomes for early T-stage ... Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2805514

Long-term Outcomes of Bevacizumab and Chemoradiation ... These findings suggest that the addition of bevacizumab to chemoradiation for nasopharyngeal cancer may be safe and tolerable.

7. ecog-acrin.org ecog-acrin.org/press-release-new-post-surgery-treament-for-hpv-throat-cancer-uses-less-radiation-safely-and-eliminates-chemotherapy/

Press Release: A new post-surgery approach for treating ... Between Arms B and C, the progression-free survival rates were statistically the same, a strong indicator that radiation alone at 50 Gy was safe ...

8. nature.com nature.com/articles/s44276-025-00164-z

Long-term outcomes of consecutive patients ... Outcomes of HPV-negative oropharyngeal cancer are dismal with 5-year overall survival (OS) of 27% to 38% [5, 11]. Recently, data from the Danish ...