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

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to find out if a personalized approach to chemoradiation therapy (which may include a lower dose of radiation) is as effective as the standard chemoradiation therapy in people with HPV-positive throat cancer. Other purposes of this study include looking at the following: * Whether a lower dose of radiation in combination with standard chemotherapy causes fewer side effects than the standard dose of radiation therapy in combination with standard chemotherapy * How the study approaches (lower dose of radiation therapy + standard chemotherapy and standard dose of radiation therapy + standard chemotherapy) affect participants' quality of life. The researchers will measure quality of life by having participants fill out questionnaires.

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.

What data supports the effectiveness of the treatment Personalized Radiation Therapy for Throat Cancer?

Research suggests that reducing the radiation dose for HPV-positive throat cancer can be effective while potentially lowering side effects. Studies have shown that this approach may maintain disease control and improve quality of life by preserving swallowing function. ^{1 2 3 4 5}

Is personalized radiation therapy generally safe for humans?

Research on de-escalated or low-dose radiation therapy, which is similar to personalized radiation therapy, has been conducted for head and neck cancers. These studies suggest that while radiation therapy can have side effects, the de-escalated approach is being explored to reduce these effects, indicating a focus on safety. ^{2 4 5 6 7}

How is Personalized Radiation Therapy different from other treatments for throat cancer?

Personalized Radiation Therapy for throat cancer is unique because it uses a lower dose of radiation tailored to the patient's specific condition, which can help maintain disease control while reducing side effects and preserving quality of life compared to standard radiation doses. ^{1 2 4 8 9}

Research Team

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

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]

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]

References

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

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. [2021]

2. Ireland 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. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Highlights from the 2021 ASCO and ESMO annual meetings on radiotherapy of head and neck cancer]. [2022]

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

Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer. [2020]

5. United States 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. [2020]

6. United States 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. [2023]

7. United States 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". [2015]

8. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy for head and neck squamous cell carcinoma: State of the art and future directions]. [2019]

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

IMRT - Biomarkers for dose escalation, dose de-escalation and personalized medicine in radiotherapy for head and neck cancer. [2019]