Personalized Radiation Therapy for Throat Cancer

Recruiting at 8 trial locations

Overseen By Nadeem Riaz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior head/neck radiation, T4 tumors, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3-5 weeks

291 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a personalized approach to radiation therapy matches the effectiveness of standard treatment for throat cancer caused by HPV, a common virus. Researchers seek to find out if a lower dose of radiation combined with standard chemotherapy results in fewer side effects and improved quality of life compared to the usual higher dose. Participants will complete questionnaires to assess their quality of life during the trial. Individuals with HPV-positive throat cancer, experiencing symptoms like difficulty swallowing or a persistent sore throat, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that a personalized approach to radiation therapy for HPV-positive throat cancer can reduce side effects while maintaining effectiveness. Studies indicate that adjusting radiation doses based on a patient's genetic makeup helps avoid the severe side effects often seen with standard treatments.

Patients without low oxygen levels in their tissues receive a lower radiation dose of 30Gy over 15 days, compared to the usual 70Gy. Early results suggest this lower dose might be just as effective in treating cancer while causing fewer side effects.

For patients with low oxygen levels, the treatment resembles the standard approach, with doses up to 70Gy. This method aims to balance effective treatment with minimizing unwanted effects.

The trial is in phase 3, indicating that earlier studies have shown the treatment is likely safe. This phase will further test how well people tolerate it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for throat cancer?

Researchers are excited about personalized radiation therapy for throat cancer because it tailors treatment based on the tumor's hypoxia status, which isn't typically done with standard treatments. Unlike the conventional approach that uses a one-size-fits-all radiation dose, this personalized method adjusts the radiation dose depending on whether the cancer is hypoxia-negative or hypoxia-positive. This could potentially reduce unnecessary radiation exposure and side effects for patients without hypoxia, while still effectively targeting more resilient tumors with a higher dose. By customizing the treatment, there's hope for improved outcomes and fewer side effects, making it a promising advancement in throat cancer care.

What evidence suggests that this trial's treatments could be effective for HPV-positive throat cancer?

Research has shown that personalized radiation therapy, which adjusts radiation doses for each patient, might be as effective as standard doses for treating HPV-positive throat cancer. In this trial, participants will join either a personalized chemoradiation therapy arm or a standard chemoradiation therapy arm. A study using genetic information suggested that adjusting radiation doses based on a person's genes can maintain high cure rates while potentially reducing side effects. Specifically, past patients with HPV-positive throat cancer experienced fewer side effects with personalized radiation therapy compared to traditional treatments. Personalized radiation therapy also aims to improve quality of life by reducing treatment intensity without losing effectiveness. These findings suggest that personalized radiation therapy could serve as a promising alternative to standard treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with HPV-positive throat cancer. Participants should be suitable for chemoradiation therapy and willing to undergo personalized treatment, which may involve a lower radiation dose. Specific eligibility criteria are not provided, but typically include factors like age, health status, and cancer stage.

Inclusion Criteria

Patient must provide study-specific informed consent prior to study entry

My blood tests within the last month show normal results.

I am fully active or able to carry out light work.

Exclusion Criteria

I have been cancer-free for 3 years or had a cancer with a 90% cure rate at 5 years.

Patients deemed non-compliant to all protocol-related activities

I have not undergone particle therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard or personalized chemoradiation therapy based on hypoxia status

3-5 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a posttreatment FDG PET/CT scan

4 months

1 visit for PET/CT scan

Long-term follow-up

Participants' overall survival is monitored over a 2-year period

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Personalized Radiation Therapy

Trial Overview

The study compares personalized chemoradiation therapy (potentially lower radiation doses) against standard chemoradiation in treating HPV-positive throat cancer. It aims to determine if the personalized approach is as effective while causing fewer side effects and impacting quality of life differently.

How Is the Trial Designed?

Group I: Personalized Chemoradiation Therapy Experimental Treatment 3 Interventions

Patient without evidence of hypoxia will receive 30Gy in 2Gy per fraction. Concurrent chemotherapy will be given as per guidelines. After completion of chemotherapy and radiation therapy, a 4 month (+/- 4 weeks) posttreatment standard FDG PET/CT scan will be performed and if there is persistent disease, standard neck dissection will be performed. Further standard of care will be given pending pathologic findings.1. Hypoxia negative: The entire target volume which includes GTV and CTV will receive 30Gy in 2 Gy per fraction over 15 days (PTV30). 2. Hypoxia positive (same as the standard of care): The CTV will receive 50Gy in 2Gy per fraction over 25 days. This is name PTV50 and will receive 50Gy in 2Gy per fraction over 25 days. The GTV will receive an additional boost of 20Gy in 2 Gy per fraction so that the total PTV70 dose is 70Gy.

Group II: Standard Chemoradiation Therapy Active Control 3 Interventions

Patient will receive 70Gy in 2Gy per fraction regardless of hypoxia status. Concurrent chemotherapy will be given as per guidelines. After completion of chemotherapy and radiation therapy, a 4 month (+/- 4 weeks) posttreatment standard FDG PET/CT scan will be performed and if there is persistent disease, standard neck dissection will be performed. Further standard of care will be given pending pathologic findings.

Personalized Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Personalized Radiation Therapy for:

• HPV-positive throat cancer

Approved in European Union as De-escalated Radiation Therapy for:

• HPV-positive oropharyngeal squamous cell carcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

The study developed the Functional Assessment of Cancer Therapy-Head and Neck Radiotherapy (FACT-HN-RAD) measure, an 8-item tool that effectively captures the most common adverse effects (AEs) of radiation therapy in patients with head and neck squamous cell carcinoma, based on input from 19 patients and 9 radiation oncologists.

Common AEs identified include difficulty swallowing, oral pain, dry mouth, and weight loss, with the measure demonstrating strong face validity among patients, indicating it accurately reflects their experiences during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer: The FACT-HN-RAD Patient-Reported Outcome Measure. Gharzai, LA., Mierzwa, ML., Peipert, JD., et al.[2023]

In a phase II trial involving 80 patients with HPV-associated oropharyngeal cancer, reducing the dose of adjuvant radiotherapy from 60-66 Gy to 30-36 Gy maintained a high locoregional tumor control rate of 96.2% over 2 years.

The study demonstrated low toxicity rates (0% grade 3 or worse toxicity post-treatment) and even slight improvements in swallowing function, indicating that this aggressive dose de-escalation approach can preserve quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. Ma, DJ., Price, KA., Moore, EJ., et al.[2021]

De-escalated radiotherapy (RT) is currently used in only 15-20% of patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) in the United States, indicating low adoption despite ongoing trials.

In HPV+ patients, de-escalated RT did not significantly affect overall survival compared to full-dose RT, with 3- and 5-year survival rates being similar, while HPV- patients showed significantly worse survival rates with de-escalated treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer. White, R., Abel, S., Hasan, S., et al.[2020]

In a study of 759 patients with HPV-positive oropharyngeal squamous cell carcinoma, dose de-escalated radiation therapy (DDRT) did not result in inferior overall survival compared to standard dose radiation therapy (SDRT), with 3-year survival rates of 82.2% for DDRT and 79.3% for SDRT (P = 0.85).

The findings suggest that reducing radiation dose in HPV-positive OPSCC patients may be safe, as there was no significant difference in survival outcomes, indicating that ongoing randomized trials are needed to further explore this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy dose de-escalation compared to standard dose radiation therapy in definitive treatment of HPV-positive oropharyngeal squamous cell carcinoma. Gabani, P., Lin, AJ., Barnes, J., et al.[2020]

Radiotherapy is crucial for treating head and neck cancer, but many patients do not achieve a complete response, highlighting the need for improved treatment strategies.

Personalized treatment approaches, including dose adjustments and systemic therapies based on individual tumor and tissue sensitivity markers, could enhance the effectiveness of radiotherapy while minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMRT - Biomarkers for dose escalation, dose de-escalation and personalized medicine in radiotherapy for head and neck cancer. Andreassen, CN., Eriksen, JG., Jensen, K., et al.[2019]

Intensity-modulated radiotherapy combined with cisplatin is recommended as the standard treatment for head and neck carcinomas, highlighting its efficacy in improving patient outcomes.

For patients unable to undergo chemotherapy, cetuximab is a viable alternative, and hyperfractionation should be considered for those unfit for standard treatments, ensuring safety and tailored approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for head and neck squamous cell carcinoma: State of the art and future directions]. Schick, U., Huguet, F., Pointreau, Y., et al.[2019]

The phase III GORTEC-REACH trial found that combining immune checkpoint inhibitors with radiotherapy for locally advanced head and neck cancer was less effective than traditional platinum-based chemoradiotherapy, although it may still be better than using EGFR inhibition alone.

Initial phase II trials suggest that dose de-escalation of radiotherapy is feasible for HPV-positive oropharyngeal cancer, but this approach should only be conducted within clinical trials to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Highlights from the 2021 ASCO and ESMO annual meetings on radiotherapy of head and neck cancer]. Hecht, M., von der Grün, J., Semrau, S., et al.[2022]

In a phase 2 clinical trial involving 60 patients with HPV-associated oropharyngeal squamous cell carcinoma, a novel deintensified radiation therapy approach resulted in a remarkable 2-year local control rate of 98.3%, indicating high efficacy in preventing cancer recurrence after surgery.

The treatment was found to be safe, with only 3.3% of patients experiencing late soft tissue necrosis that resolved quickly, and no patients required feeding tubes during or after treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed After Transoral Robotic Surgery for Human Papilloma Virus-Related Squamous Cell Carcinoma of the Oropharynx. Swisher-McClure, S., Lukens, JN., Aggarwal, C., et al.[2020]

In a study of 133 children and adolescents who received radiotherapy to the salivary glands, it was found that both acute and late side effects were significantly influenced by the maximum radiation dose, with higher doses leading to increased toxicity.

For every 1 Gray increase in radiation dose to the submandibular glands, there was a 4% increase in the odds of acute toxicities, highlighting the importance of dose management in minimizing side effects in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the "Registry for the evaluation of side effects after radiotherapy in childhood and adolescence". Bölling, T., Weege, J., Eich, HT., et al.[2015]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12216805/

De‐escalation of radiotherapy in the treatment of human ...

To evaluate the benefits and harms of de‐escalation of radiotherapy compared with standard radiotherapy in the treatment of human papillomavirus‐associated ...

2.

jci.org

jci.org/articles/view/198351

Genomic adjusted radiation dose stratifies radiotherapy ...

Uniform radiation therapy (RT) de-escalation in HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has underperformed in clinical trials, likely ...

3.

lerner.ccf.org

lerner.ccf.org/news/article/?title=New+study+supports+gene-tailored+radiation+doses+to+treat+HPV%2B+throat+cancer+&id=f5def6234a1c662cd3c5d745e7da5fac2f2c3fdd

New study supports gene-tailored radiation doses to treat ...

Genomic model shows promise in tailoring radiation doses, potentially reducing side effects without compromising cure rates.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0360301625061887

A Population-Based Cohort Study Using the Swedish Head ...

Despite their improved outcomes, patients remain labored with the acute and late side effects of treatment from intensive courses of radiation ...

5.

practicalradonc.org

practicalradonc.org/article/S1879-8500(24)00139-5/fulltext

Radiation Therapy for HPV-Positive Oropharyngeal ...

Cervical nodal level V can safely be omitted in the treatment of locally advanced oropharyngeal squamous cell carcinoma with definitive IMRT.

6.

astro.org

astro.org/news-and-publications/news-and-media-center/news-releases/2024/astro-issues-clinical-guideline-on-radiation-therapy-for-patients-with-hpv-related-throat-cancer

ASTRO issues clinical guideline on radiation therapy ...

ASTRO issues clinical guideline on radiation therapy for patients with HPV-related throat cancer. Update to 2017 guideline focuses on ...