De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA

ConditionsClinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma Stage I Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage II Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorMayo Clinic

About this trial

This phase II trial examines the use of blood-based biomarkers is to help inform decision making for treatment and radiation therapy for patients with human papillomavirus (HPV) positive oropharyngeal squamous cell cancers. The standard treatments for head and neck cancers are radiation therapy with chemotherapy or surgery potentially followed by radiation therapy with or without chemotherapy. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving chemotherapy along with radiation may kill more tumor cells. However, the cancer can recur or can spread to other parts of the body and all treatments can be associated with side effects. The purpose of this study is to evaluate a blood-based biomarker, using the NavDx testing device, for head and neck cancers in order to see if it can help improve selection of the intensity of treatment in order to best balance the side effects of treatment with the goal of decreasing cancer recurrence. This test could aid in early detection of recurrence and salvage therapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

PRE-REGISTRATION (optional): Provide written informed consent

Age >= 18 years

Histological confirmation of squamous cell carcinoma originating from or suspected to be originating from the oropharynx

Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy with cisplatin. Note: The patient must be cisplatin eligible even if an alternate is used due to drug shortage

Disqualifiers

Pregnant women

Nursing women

Men or women of childbearing potential who are unwilling to employ adequate contraception

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Trial design

Design model

Parallel

Treatments tested in this trial

Biospecimen Collection
Procedure/Surgery
Undergo blood and saliva specimen collection for NavDx testing
Cisplatin
Drug
Given IV
Computed Tomography
Procedure/Surgery
Undergo CT scan
Diffusing Alpha-emitter Radiation Therapy
Radiation
Undergo DART
Docetaxel
Drug
Given IV
Intensity-Modulated Proton Therapy
Procedure/Surgery
Undergo IMPT
Intensity-Modulated Radiation Therapy
Radiation
Undergo IMRT
Magnetic Resonance Imaging
Procedure/Surgery
Undergo MRI
Modified Barium Swallow Study
Procedure/Surgery
Undergo MBSS
Observation Activity
Other intervention
Undergo observation
Positron Emission Tomography
Procedure/Surgery
Undergo PET scan
Quality-of-Life Assessment
Other intervention
Ancillary studies
Questionnaire
Other intervention
Ancillary studies

Treatment groups

455 Participants

are divided into 4 treatment groups

Group A: Group 1 (observation)Active comparator 8 interventions

Group B: Group 2 (DART, docetaxel)Experimental treatment 9 interventions

Group C: Group 3 (IMRT/IMPT, with/without cisplatin)Experimental treatment 10 interventions

Group D: Group 4 (IMRT/IMPT, cisplatin)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

Progression-free survival (PFS)

Progression-free survival (PFS), the time from treatment initiation until disease progression or worsening. PFS at specific timepoints will be estimated using Kaplan-Meier methodology.

Time frame

From registration to the first of either disease progression/recurrence or death, assessed up to 5 years

Secondary outcomes

Progression-free survival (PFS) follow-up

Progression-free survival (PFS) is defined as the time from treatment initiation until disease progression or worsening. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response versus (vs.) no response), we'll use logistic regression models.

Time frame

At years 1, 2, 3, 4, and 5

Disease-free survival (DFS)

Disease-free survival (DFS) is the measure of time after treatment during which no sign of cancer is found. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

From time of surgery and also from end of all treatment across all the groups, assessed up to 5 years

Overall survival (OS)

Overall survival (OS) is defined as the duration of patient survival from the time of treatment initiation. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

At years 1, 2, 3, 4, and 5

Patient reported outcomes (PROs)

Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

Up to 5 years

Other outcomes

ctHPVDNA detectability

Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

At post-operative day 1 or 2

Salivary ctHPVDNA analysis for recurrence risk and surveillance

Salivary samples will be analyzed pre-treatment, post-op, and at the time of recurrence to determine whether salivary ctHPVDNA may further inform recurrence risk and surveillance in HPV(+) oropharyngeal squamous cell carcinoma. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

Up to 5 years

Characterization of post-operative drain fluid

We will characterize post-operative drain fluid and compare rates of detectability to blood and saliva in order with the aim to determine whether the regional drain represents a separate regional compartment for analysis. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

Up to 5 years

Quantification of pre-treatment imaging

We will prospectively quantify pretreatment imaging for number of involved nodes, radiographic extranodal extension as it relates to pathologic findings and risk of recurrence. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.

Time frame

Up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

Source ClinicalTrials.gov

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