HPV DNA-Guided Radiotherapy De-intensification of Head and Neck Squamous Cell Carcinoma

Squamous Cell Carcinoma of the Oropharynx Clinical Trial

— HN001  

Official title:

Circulating Tumor Modified HPV DNA-Guided Radiotherapy De-intensification of the Elective Neck (RaDEN) in Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05962242
• Other study ID #: HSR220263
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2024
• Est. completion date: November 1, 2029

Study information

• Verified date: December 2023
• Source: University of Virginia
• Contact: Song W
• Phone: 434-243-0008
• Email: UVARADONCClinicalTrials[@]uvahealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the safety and effectiveness of a lower than standard dose of radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.

Description:

In squamous cell carcinomas of the head and neck, regional recurrence is rare within lymph node stations treated with elective radiation. However, radiotherapy to the neck is toxic, and leads to a variety of unpleasant side effects, especially coupled with concurrent systemic therapy. There is growing evidence from previous studies showing that lower radiation doses may be adequate in preventing locoregional recurrence of disease. The hypothesis is that lower dose of radiation will have equal effectiveness but less toxicity than standard approaches for the treatment of squamous cell carcinomas of the head and neck. The study evaluates the effectiveness and safety of reduced dose radiotherapy for definitive and adjuvant treatment of Human papillomavirus (HPV) positive oropharyngeal squamous cell carcinomas. Participants will be treated with a radiation therapy regimen that has a lower dose to less tissue area (dose and volume de-escalation) than standard of care radiation therapy. The dosing will be determined by whether concurrent chemotherapy will be given, results from on treatment HPV blood test called NavDx, physical exam, and imaging. On treatment NavDx results indicating a slow (non-rapid) response to the treatment will receive an additional boost of radiation. Routine NavDx testing will be performed to assess treatment response and recurrence. Participants will also be asked to complete surveys about overall health and wellbeing.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: November 1, 2029
• Est. primary completion date: November 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, = 18 years of age

4. Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any AJCC 8th edition stage.

5. Eligible for and planning to receive definitive treatment or adjuvant treatment with radiotherapy.

6. Participants who are receiving concurrent systemic anticancer therapy (e.g. chemotherapy or immunotherapy) for oropharyngeal cancer are eligible.

1. For participants with T1-2 and N0 disease, chemotherapy is not required for eligibility. Participants may or may not receive chemotherapy per physician discretion.

2. For participants with T3-4 and/or N+ disease, chemotherapy is required for eligibility.

7. Participants may receive investigational agents with prior approval from the Principal Investigator.

8. ECOG Performance Status of 0-2.

9. p16 positive HPV as determined by NavDx and immunohistochemistry

10. For females of reproductive potential: agreement to use adequate contraception during radiation treatment and for 6 months (or more if applicable based on other medications) after the end of radiation treatment.

Exclusion Criteria:

1. Evidence of distant metastatic disease

2. Prior history of radiotherapy to the head and/or neck

3. Had surgery for oropharyngeal cancer within 8 months of enrollment.

4. Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.

5. Diagnosis of a current or prior invasive malignancy (except non-melanoma skin cancer) unless the participant has been disease free for at least 3 years.

6. Participant is a prisoner

7. Known contraindications to head and neck radiation therapy such as ataxia telangiectasia or scleroderma.

8. Pregnancy or lactation

9. Active or severe co-morbidities as defined by the following:

1. Unstable angina and/or congestive heart failure requiring hospitalization up to 180 days before registration

2. Transmural myocardial infarction up to 180 days before registration

3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

5. Hepatic insufficiency as determined by the treating clinician resulting in clinical jaundice and/or coagulation effects or severe liver dysfunction.

6. Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be slightly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

10. Tobacco smoking history of 10 pack years or greater, or = 20 pack years if smoking cessation occurred at least 1 year prior to enrollment

11. Current use of antineoplastic drugs for other malignancies.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of the Oropharynx

Intervention

Radiation:
• Radiation Therapy
External Beam Radiation to Head and Neck

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia
United States	Miami Cancer Institute	Miami	Florida
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To estimate long-term survival for participants treated with dose and volume-de-escalated radiotherapy to the neck	Overall survival	up to 5 years after radiotherapy
Other	To estimate the relationship between baseline lymphocyte counts and disease progression outcomes.	Baseline lymphocyte counts from CBC with Differential blood test	up to 2 years after radiotherapy
Other	To estimate the relationship between baseline lymphocyte counts and disease progression	Occurrence of disease progression	up to 2 years after radiotherapy
Primary	To assess the disease control of participants who receive dose and volume-de-escalated radiotherapy to the neck, guided by treatment response through circulating tumor-modified HPV DNA testing	Incidence of disease free survival as measured by circulating HPV on Nav Dx blood tests.	up to 2 years after radiotherapy
Secondary	To assess safety for treatment with reduced dose and volume-de-escalated radiotherapy to the neck	Incidence of grade 3 (or greater) adverse events as defined by the CTCAE v5.0	Evaluated through 6 months and 1 year post- radiation.
Secondary	To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck	Quality of life as determined by the EORTC H&N35. Questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level.	up to 2 years after radiotherapy
Secondary	To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck	Quality of life as determined by the EORTC QLQ-C30. Majority of questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level. Two questions are scaled from 1-7 with 1 meaning very poor (worse outcome) and 7 meaning excellent (best outcome).	up to 2 years after radiotherapy