Low-Dose Chemoradiotherapy for Oropharyngeal Cancer

Overseen By John Botzler

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Pregnancy, Other malignancies, Neuropathy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a low-dose combination of chemotherapy and radiation for individuals with advanced HPV-positive oropharyngeal cancer, a throat cancer linked to the human papillomavirus. Researchers aim to determine if this lower-dose therapy is effective and causes fewer side effects than standard treatments. Participants must have a diagnosis of HPV-positive throat cancer and should not have undergone previous treatments such as surgery or chemotherapy. As an unphased trial, this study provides participants the chance to contribute to innovative research that could lead to improved treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on any other anticancer therapy while participating in this trial.

What prior data suggests that this low-dose chemoradiotherapy is safe for oropharyngeal cancer patients?

Research has shown that low-dose chemoradiotherapy for HPV-positive oropharyngeal cancer can be safe for patients. However, some patients experience side effects, such as serious mouth problems. These treatments involve radiation over several weeks, which can sometimes lead to difficulties like needing a feeding tube.

Overall, survival rates for those with advanced stages of this cancer are encouraging, with five-year survival rates between 75-80%. While there are risks, many patients handle the treatment well and achieve positive outcomes. Prospective participants should consider this information when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the low-dose chemoradiotherapy approach for oropharyngeal cancer because it aims to reduce the intensity of radiation treatment while maintaining effectiveness. Traditional treatments often involve higher doses of radiation, which can lead to significant side effects. This study uses intensity-modulated radiotherapy (IMRT) with lower doses, specifically PTV50.4 and PTV56, delivered five days a week. The potential benefits include fewer side effects and a better quality of life for patients, making this method a promising advancement in cancer care.

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

Research has shown that using lower doses of combined chemotherapy and radiation can safely treat HPV-positive throat cancer. In this trial, all participants will receive reduced-dose radiation treatment with intensity-modulated radiotherapy (IMRT) using PTV56 and PTV50.4. Some patients have experienced serious mouth problems as side effects, but this method aims to reduce these compared to higher doses. Early results suggest that while this treatment can be effective, it might not prevent cancer recurrence within two years as successfully as the standard treatment. These studies help doctors balance treatment effectiveness with side effects, guiding future treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Marshall R. Posner

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults over 18 with HPV+ oropharyngeal cancer that's not been treated before can join. They need a biopsy for testing, no heavy alcohol use in the last 6 months, and good organ function. Pregnant women, those unwilling to use contraception, people with other cancers (except certain types), severe neuropathy or hearing loss, lung disease, recent heart attack or serious illness can't participate.

Inclusion Criteria

My cancer is HPV positive and located in the throat, nasal area, or related regions.

No active alcohol addiction (as assessed by medical caregiver and defined as at least 6 months without activity)

My liver, kidneys, and bone marrow are functioning well.

Exclusion Criteria

I have lost more than 25% of my weight without trying in the last 2 months.

Participation in an investigational therapeutic drug trial within 30 days of study entry

Active smoking or a cumulative pack year history of > 20 pack years, active smoking is (Defined as ≥ 1 cigarette per day) within the last 5 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy to establish efficacy and toxicity before chemoradiotherapy

6-8 weeks

Reduced Dose Chemoradiotherapy

Participants receive daily radiation treatment with intensity-modulated radiotherapy (IMRT) for 5 days per week

6-7 weeks

Follow-up

Participants are monitored for safety, effectiveness, and long-term toxicity after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• PTV50.4
• PTV56

Trial Overview The trial is testing if lower doses of chemoradiotherapy after initial chemotherapy are effective and safe for advanced HPV-related throat cancer patients. It also aims to identify factors predicting who benefits from this approach.

How Is the Trial Designed?

Group I: Reduced Dose Radiation Experimental Treatment 2 Interventions

All patients will receive daily radiation treatment with intensity-modulated radiotherapy (IMRT) - PTV56 and PTV50.4. Treatment will be given 5 days per week and will not routinely be delivered on Saturday, Sunday or major holidays unless a treatment is missed during the week due to technical and/or medical reasons. No more than 5 treatments should be given per week.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Patients with HPV-positive oropharyngeal cancer who underwent risk- and response-adapted de-escalated radiation therapy (RT) and chemoradiation (CRT) showed significantly better functional outcomes, including improved swallowing function and higher body mass index (BMI), compared to those receiving standard high-dose treatment.

The study found that lower treatment intensity (RT50/CRT45) was associated with less PEG-tube dependency and reduced narcotic use, highlighting the benefits of de-escalation in treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes. Foster, CC., Seiwert, TY., MacCracken, E., et al.[2021]

In a phase 2 trial involving 45 patients with HPV-positive oropharyngeal cancer, de-escalated chemoradiation therapy resulted in a low rate of gastrostomy tube placement (5%) and allowed 95% of patients to return to a normal diet after treatment, indicating improved functional outcomes.

Patients who had a normal BMI before treatment were able to recover to baseline BMI levels approximately 18 months post-therapy, suggesting that the treatment approach may help maintain nutritional status and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial. Hegde, JV., Shaverdian, N., Felix, C., et al.[2019]

In a study of 421 patients with HPV-associated oropharyngeal squamous cell carcinoma, high-dose cisplatin (HDC) showed better outcomes for stage III disease, including lower rates of locoregional recurrence and distant metastasis, as well as improved overall survival compared to triweekly carboplatin (TC).

However, HDC was associated with significantly higher toxicity, including increased rates of severe leukopenia and weight loss, suggesting that TC may be a safer option for patients with early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer. Iganej, S., Beard, BW., Chen, J., et al.[2020]

A de-escalation strategy of reduced adjuvant radiation and chemotherapy after surgery for HPV-positive oropharyngeal cancer resulted in low long-term toxic effects, with only 1.4% experiencing grade 2 toxic effects at 1 year and no grade 4-5 toxic effects reported.

Patients showed significant improvements in swallow function and quality of life over time, with most returning to baseline levels, indicating that this treatment approach is both effective and preserves patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Toxic Effects, Swallow Function, and Quality of Life on MC1273: A Phase 2 Study of Dose De-escalation for Adjuvant Chemoradiation in Human Papillomavirus-Positive Oropharyngeal Cancer. Price, K., Van Abel, KM., Moore, EJ., 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]

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]

Citations

1. withpower.com withpower.com/trial/phase-oropharyngeal-neoplasms-3-2016-dd985

Low-Dose Chemoradiotherapy for Oropharyngeal Cancer Studies on low-dose chemoradiotherapy for HPV-positive oropharyngeal cancer show it can be safe, with some patients experiencing side effects like severe mouth ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02945631

Quarterback 2b - Sequential Therapy With Reduced Dose ... The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301616328073

Methods for Reducing Normal Tissue Complication ... The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 ...

4. 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.

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6460765/

HPV-driven oropharyngeal cancer: current knowledge of ... Five-year survival rates for patients with advanced stage HPV(+) OPSCC are 75–80%, versus survival rates of less than 50% among patients with ...

7. journal.waocp.org journal.waocp.org/article_91136_da9eb15958def6d9171543516d8c1e2d.pdf

research article - Asian Pacific Journal of Cancer Prevention Multiple planned target volumes (PTVs) can now be treated in a single plan using advances in radiation.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2405632420300032

Clinical and dosimetric risk stratification for patients at high- ... The purpose of this study was to identify organs to which dose limitation using IMRT can potentially modify the incidence and duration of feeding tube-use.