Ignite Creation Date:
2025-12-26 @ 11:49 AM
Ignite Modification Date:
2025-12-26 @ 11:49 AM
Study NCT ID:
NCT05541016
Status:
RECRUITING
Last Update Posted:
2025-11-04
First Post:
2022-08-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA
Sponsor:
Mayo Clinic
Organization:
Study Overview
Official Title:
DART 2.0: ctHPV-DNA Informed De-Escalated Adjuvant and Definitive Radiation Therapy
Status:
RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
PRIMARY OBJECTIVES:
I. To prospectively incorporate circulating tumor human papillomavirus deoxyribonucleic acid (ctHPVDNA) in combination with clinical and pathologic factors to appropriately select patients for treatment intensity.
II. To demonstrate patients traditionally offered adjuvant radiation therapy (RT) but at low risk of treatment failure based on clinical pathologic and post op ctHPVDNA risk factors have an acceptable 1-year progression free survival (PFS) warranting further study. (Favorable Intermediate Risk \[GROUP 1\]) III. To demonstrate based on clinical, pathologic, and ctHPVDNA risk factors a select population receiving diffusing alpha-emitter radiation therapy (DART) (+ multiple segment radiation therapy \[MSRT\] where applicable) is associated with acceptable 2 year PFS. (Unfavorable Intermediate Risk \[GROUP 2\]) IV. To quantify the rate of recurrence as defined by the 2 year PFS in an identified high risk population using the incorporation of ctHPVDNA. (High Risk \[GROUP 3\]) V. To prospectively use week 4 ctHPVDNA to guide treatment intensity of 56 versus (vs) 70 Gy with concurrent cisplatin to demonstrate 56 Gy with sufficient ctHPVDNA clearance results in an acceptable 2 year PFS. (Chemoradiation Cohort \[GROUP 4\])
SECONDARY OBJECTIVES:
I. To compare PFS by treatment arm including at landmark timepoints II. To assess the disease-free survival (DFS) in patients that are disease-free post-treatment.
III. To compare overall survival (OS) by treatment arm including at landmark timepoints.
IV. To compare patient reported outcomes (PROS) by treatment arm and modality. V. To evaluate treatment toxicity by Common Terminology Criteria for Adverse Events (CTCAE) criteria as rated by providers across treatment arms.
VI. To define patterns of recurrence by treatment arm. VII. To describe salvage therapy by treatment arm, including the rate, type, and success of salvage treatment.
VIII. To compare functional outcomes by treatment arm based on modified barium swallow study (MBSS) and Functional Oral Intake Scale (FOIS) by treatment arm.
IX. To return to work parameters by treatment arm as assessed by the Work Productivity and Activity Impairment Questionnaire (WPAI).
X. To quantify the costs of return visits for surveillance. XI. To assess end of treatment ctHPVDNA detectability and its association with PFS by comparing patients with detectable versus undetectable end of treatment ctHPVDNA within treatment arms.
XII. To compare outcomes by institution. XIII. To evaluate rates of post operative bleeding, tracheostomy, and readmission with 6 weeks of resection.
XIV. To compare methods of surveillance in diagnosis of recurrence including clinical evaluation, ctHPVDNA testing, and imaging.
XV. To investigate the impact of tobacco and smoking history on recurrence, PFS, and OS.
XVI. To perform a matched analysis of patients by clinical and pathologic risk factors to MC1273, MC1675, and MC Mucosal Sparing (NCT02736786).
CORRELATIVE RESEARCH OBJECTIVES:
I. Will investigate post-op Day 1 or 2 ctHPVDNA detectability as a surrogate for detectability for later post-op timepoints including risk of recurrence rates.
II. Will analyze salivary samples 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 (OPSCC).
III. 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.
IV. Will prospectively quantify pretreatment imaging for number of involved nodes, radiographic extranodal extension (rENE) as it relates to pathologic findings and risk of recurrence.
V. Will analyze within category of low intermediate, high intermediate, and high-risk patients the percentage of tumor infiltrating lymphocytes (TILs) and association with recurrence as well as differences across treatment groups.
VI. Will assess whether HPV is integrated vs episomal for each patient and the relationship of ctHPVDNA detectability and outcomes.
VII. Will investigate molecular markers on formalin-fixed paraffin-embedded (FFPE) from primary surgical specimens.
OUTLINE: Patients are assigned to 1 of 4 groups.
GROUP I: Patients undergo observation following standard of care surgery. Patients undergo MBSS at pre-operative (pre-op), 2 weeks post-operative (post-op), and 3 months follow-up. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
GROUP II: Patients undergo DART with/without mucosal sparing twice daily (BID) on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel intravenously (IV) over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
GROUP III: Patients undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) once daily (QD) on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week (QW) on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
GROUP IV: Patients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at prior to RT, at the end of RT, at any clinical recurrence.
After completion of study treatment, patients are followed up at 4-6 weeks post treatment, every 3 months post-treatment for 2 years, every 6 months for year 3, and annually for years 4 and 5.
I. To prospectively incorporate circulating tumor human papillomavirus deoxyribonucleic acid (ctHPVDNA) in combination with clinical and pathologic factors to appropriately select patients for treatment intensity.
II. To demonstrate patients traditionally offered adjuvant radiation therapy (RT) but at low risk of treatment failure based on clinical pathologic and post op ctHPVDNA risk factors have an acceptable 1-year progression free survival (PFS) warranting further study. (Favorable Intermediate Risk \[GROUP 1\]) III. To demonstrate based on clinical, pathologic, and ctHPVDNA risk factors a select population receiving diffusing alpha-emitter radiation therapy (DART) (+ multiple segment radiation therapy \[MSRT\] where applicable) is associated with acceptable 2 year PFS. (Unfavorable Intermediate Risk \[GROUP 2\]) IV. To quantify the rate of recurrence as defined by the 2 year PFS in an identified high risk population using the incorporation of ctHPVDNA. (High Risk \[GROUP 3\]) V. To prospectively use week 4 ctHPVDNA to guide treatment intensity of 56 versus (vs) 70 Gy with concurrent cisplatin to demonstrate 56 Gy with sufficient ctHPVDNA clearance results in an acceptable 2 year PFS. (Chemoradiation Cohort \[GROUP 4\])
SECONDARY OBJECTIVES:
I. To compare PFS by treatment arm including at landmark timepoints II. To assess the disease-free survival (DFS) in patients that are disease-free post-treatment.
III. To compare overall survival (OS) by treatment arm including at landmark timepoints.
IV. To compare patient reported outcomes (PROS) by treatment arm and modality. V. To evaluate treatment toxicity by Common Terminology Criteria for Adverse Events (CTCAE) criteria as rated by providers across treatment arms.
VI. To define patterns of recurrence by treatment arm. VII. To describe salvage therapy by treatment arm, including the rate, type, and success of salvage treatment.
VIII. To compare functional outcomes by treatment arm based on modified barium swallow study (MBSS) and Functional Oral Intake Scale (FOIS) by treatment arm.
IX. To return to work parameters by treatment arm as assessed by the Work Productivity and Activity Impairment Questionnaire (WPAI).
X. To quantify the costs of return visits for surveillance. XI. To assess end of treatment ctHPVDNA detectability and its association with PFS by comparing patients with detectable versus undetectable end of treatment ctHPVDNA within treatment arms.
XII. To compare outcomes by institution. XIII. To evaluate rates of post operative bleeding, tracheostomy, and readmission with 6 weeks of resection.
XIV. To compare methods of surveillance in diagnosis of recurrence including clinical evaluation, ctHPVDNA testing, and imaging.
XV. To investigate the impact of tobacco and smoking history on recurrence, PFS, and OS.
XVI. To perform a matched analysis of patients by clinical and pathologic risk factors to MC1273, MC1675, and MC Mucosal Sparing (NCT02736786).
CORRELATIVE RESEARCH OBJECTIVES:
I. Will investigate post-op Day 1 or 2 ctHPVDNA detectability as a surrogate for detectability for later post-op timepoints including risk of recurrence rates.
II. Will analyze salivary samples 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 (OPSCC).
III. 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.
IV. Will prospectively quantify pretreatment imaging for number of involved nodes, radiographic extranodal extension (rENE) as it relates to pathologic findings and risk of recurrence.
V. Will analyze within category of low intermediate, high intermediate, and high-risk patients the percentage of tumor infiltrating lymphocytes (TILs) and association with recurrence as well as differences across treatment groups.
VI. Will assess whether HPV is integrated vs episomal for each patient and the relationship of ctHPVDNA detectability and outcomes.
VII. Will investigate molecular markers on formalin-fixed paraffin-embedded (FFPE) from primary surgical specimens.
OUTLINE: Patients are assigned to 1 of 4 groups.
GROUP I: Patients undergo observation following standard of care surgery. Patients undergo MBSS at pre-operative (pre-op), 2 weeks post-operative (post-op), and 3 months follow-up. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
GROUP II: Patients undergo DART with/without mucosal sparing twice daily (BID) on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel intravenously (IV) over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
GROUP III: Patients undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) once daily (QD) on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week (QW) on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
GROUP IV: Patients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at prior to RT, at the end of RT, at any clinical recurrence.
After completion of study treatment, patients are followed up at 4-6 weeks post treatment, every 3 months post-treatment for 2 years, every 6 months for year 3, and annually for years 4 and 5.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
True
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: