HN001: HPV DNA-Guided Radiotherapy De-intensification of Head and Neck Squamous Cell Carcinoma

Sponsor

University of Virginia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05962242

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

22.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Oropharynx	Radiation: Radiation Therapy	Phase 2

Detailed 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 and results from on treatment HPV blood test called NavDx. 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants on this study will undergo a reduced dose regimen starting with a boost to gross disease of 24 Gy, then 30-36 Gy to entire volume based on the plan for concurrent chemotherapy. Non-responders will receive a boost to the entire volume for an additional 10 Gy.Participants on this study will undergo a reduced dose regimen starting with a boost to gross disease of 24 Gy, then 30-36 Gy to entire volume based on the plan for concurrent chemotherapy. Non-responders will receive a boost to the entire volume for an additional 10 Gy.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2027

Anticipated Study Completion Date :

Sep 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.	Radiation: Radiation Therapy External Beam Radiation to Head and Neck
Experimental: Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume.	Radiation: Radiation Therapy External Beam Radiation to Head and Neck
Experimental: Reduce Dose without Concurrent Chemotherapy Rapid Responder A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume.	Radiation: Radiation Therapy External Beam Radiation to Head and Neck
Experimental: Reduce Dose with Concurrent Chemotherapy Rapid Responder A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume.	Radiation: Radiation Therapy External Beam Radiation to Head and Neck

Outcome Measures

Primary Outcome Measures

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 [up to 2 years after radiotherapy]
Incidence of disease free survival as measured by circulating HPV on Nav Dx blood tests.

Secondary Outcome Measures

To assess safety for treatment with reduced dose and volume-de-escalated radiotherapy to the neck [Evaluated through 6 months and 1 year post- radiation.]
Incidence of grade 3 (or greater) adverse events as defined by the CTCAE v5.0
To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck [up to 2 years after radiotherapy]
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.
To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck [up to 2 years after radiotherapy]
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).

Other Outcome Measures

To estimate long-term survival for participants treated with dose and volume-de-escalated radiotherapy to the neck [up to 5 years after radiotherapy]
Overall survival
To estimate the relationship between baseline lymphocyte counts and disease progression outcomes. [up to 2 years after radiotherapy]
Baseline lymphocyte counts from CBC with Differential blood test
To estimate the relationship between baseline lymphocyte counts and disease progression [up to 2 years after radiotherapy]
Occurrence of disease progression

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, ≥ 18 years of age
Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any AJCC 8th edition stage.
Eligible for and planning to receive definitive treatment or adjuvant treatment with radiotherapy.
Participants who are receiving concurrent systemic anticancer therapy (e.g. chemotherapy or immunotherapy) for oropharyngeal cancer are eligible.
For participants with T1-2 and N0 disease, chemotherapy is not required for eligibility. Participants may or may not receive chemotherapy per physician discretion.
For participants with T3-4 and/or N+ disease, chemotherapy is required for eligibility.
Participants may receive investigational agents with prior approval from the Principal Investigator.
ECOG Performance Status of 0-2.
p16 positive HPV as determined by NavDx
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:

Evidence of distant metastatic disease
Prior history of radiotherapy to the head and/or neck
Had surgery for oropharyngeal cancer within 8 months of enrollment.
Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.
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.
Participant is a prisoner
Known contraindications to head and neck radiation therapy such as ataxia telangiectasia or scleroderma.
Pregnancy or lactation
Active or severe co-morbidities as defined by the following:
Unstable angina and/or congestive heart failure requiring hospitalization up to 180 days before registration
Transmural myocardial infarction up to 180 days before registration
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
Hepatic insufficiency as determined by the treating clinician resulting in clinical jaundice and/or coagulation effects or severe liver dysfunction.
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.
Tobacco smoking history of 10 pack years or greater, or ≥ 20 pack years if smoking cessation occurred at least 1 year prior to enrollment
Current use of antineoplastic drugs for other malignancies.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miami Cancer Institute	Miami	Florida	United States	33176
2	University of Virginia	Charlottesville	Virginia	United States	22908
3	Eastern Virginia Medical School	Norfolk	Virginia	United States	23507
4	Virginia Commonwealth University	Richmond	Virginia	United States	23284