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

43 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment PTV50.4, PTV56 for oropharyngeal cancer?

Research shows that reducing the dose of chemoradiation (a combination of chemotherapy and radiation therapy) for HPV-positive oropharyngeal cancer can lead to good functional outcomes and quality of life, while still being effective. This suggests that lower doses, like those in PTV50.4 and PTV56, might be beneficial for patients. ^{1 2 3 4 5}

Is low-dose chemoradiotherapy for oropharyngeal cancer safe?

Studies on low-dose chemoradiotherapy for HPV-positive oropharyngeal cancer show it can be safe, with some patients experiencing side effects like severe mouth sores and difficulty swallowing. However, these side effects are generally less severe compared to standard treatments, and long-term follow-up is needed to confirm safety. ^{2 6 7 8 9}

How does the treatment PTV50.4, PTV56 for oropharyngeal cancer differ from other treatments?

This treatment involves a lower dose of chemoradiotherapy, which means using less radiation and chemotherapy than standard treatments. This approach aims to reduce long-term side effects while maintaining effectiveness, especially for patients with human papillomavirus-positive oropharyngeal cancer. ^{1 2 3 4 10}

What is the purpose of this trial?

The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally advanced HPV+ oropharynx cancer and establish prognostic factors that would apply to help select patients for this treatment in the future.

Research Team

Marshall R. Posner

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. United States 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. [2019]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Radiotherapy dose and survival outcomes in human papillomavirus positive oropharyngeal cancer. [2020]

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

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes. [2021]

5. England 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. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Weight Loss and Percutaneous Endoscopic Gastrostomy Tube Placement during Chemoradiotherapy for Locally Advanced Cancer of the Oropharynx Do Not Negatively Impact Outcomes. [2022]

7. England pubmed.ncbi.nlm.nih.gov

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Regional control is preserved after dose de-escalated radiotherapy to involved lymph nodes in HPV positive oropharyngeal cancer. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer. [2020]