Trial Title:
De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA
NCT ID:
NCT05541016
Condition:
Oropharyngeal Human Papillomavirus-Positive Squamous Cell Carcinoma
Clinical 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
Conditions: Official terms:
Carcinoma
Oropharyngeal Neoplasms
Cisplatin
Docetaxel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and saliva specimen collection for NavDx testing
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Given IV
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
Abiplatin
Other name:
Blastolem
Other name:
Briplatin
Other name:
CDDP
Other name:
Cis-diammine-dichloroplatinum
Other name:
Cis-diamminedichloridoplatinum
Other name:
Cis-diamminedichloro Platinum (II)
Other name:
Cis-diamminedichloroplatinum
Other name:
Cis-dichloroammine Platinum (II)
Other name:
Cis-platinous Diamine Dichloride
Other name:
Cis-platinum
Other name:
Cis-platinum II
Other name:
Cis-platinum II Diamine Dichloride
Other name:
Cismaplat
Other name:
Cisplatina
Other name:
Cisplatinum
Other name:
Cisplatyl
Other name:
Citoplatino
Other name:
Citosin
Other name:
Cysplatyna
Other name:
DDP
Other name:
Lederplatin
Other name:
Metaplatin
Other name:
Neoplatin
Other name:
Peyrone's Chloride
Other name:
Peyrone's Salt
Other name:
Placis
Other name:
Plastistil
Other name:
Platamine
Other name:
Platiblastin
Other name:
Platiblastin-S
Other name:
Platinex
Other name:
Platinol
Other name:
Platinol- AQ
Other name:
Platinol-AQ
Other name:
Platinol-AQ VHA Plus
Other name:
Platinoxan
Other name:
Platinum
Other name:
Platinum Diamminodichloride
Other name:
Platiran
Other name:
Platistin
Other name:
Platosin
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Other name:
Computerized axial tomography (procedure)
Intervention type:
Radiation
Intervention name:
Diffusing Alpha-emitter Radiation Therapy
Description:
Undergo DART
Arm group label:
Group 2 (DART, docetaxel)
Other name:
DaRT
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Given IV
Arm group label:
Group 2 (DART, docetaxel)
Other name:
Docecad
Other name:
RP56976
Other name:
Taxotere
Other name:
Taxotere Injection Concentrate
Other name:
RP 56976
Other name:
RP-56976
Intervention type:
Procedure
Intervention name:
Intensity-Modulated Proton Therapy
Description:
Undergo IMPT
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
IMPT
Intervention type:
Radiation
Intervention name:
Intensity-Modulated Radiation Therapy
Description:
Undergo IMRT
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
IMRT
Other name:
Intensity Modulated RT
Other name:
Intensity-Modulated Radiotherapy
Other name:
Radiation, Intensity-Modulated Radiotherapy
Other name:
Intensity modulated radiation therapy (procedure)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
Magnetic resonance imaging (procedure)
Intervention type:
Procedure
Intervention name:
Modified Barium Swallow Study
Description:
Undergo MBSS
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
MBS
Other name:
Modified Barium Swallow
Other name:
VFSS
Other name:
Videofluoroscopic Swallowing Study
Intervention type:
Other
Intervention name:
Observation
Description:
Undergo observation
Arm group label:
Group 1 (observation)
Other name:
Inspection
Other name:
Visual Inspection
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET scan
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
Positron emission tomography (procedure)
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Arm group label:
Group 4 (IMRT/IMPT, cisplatin)
Other name:
Quality of Life Assessment
Intervention type:
Other
Intervention name:
Questionnaire
Description:
Ancillary studies
Arm group label:
Group 1 (observation)
Arm group label:
Group 2 (DART, docetaxel)
Arm group label:
Group 3 (IMRT/IMPT, with/without cisplatin)
Other name:
Questionnaire Administration
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 assess 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- PRE-REGISTRATION (optional): Provide written informed consent
- Age >= 18 years
- Histological confirmation of p16+ OPSCC or HPV(+) OPSCC
- 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
- Absence of distant metastases on standard diagnostic work-up =< 16 weeks prior to
registration. (Chest CT or PET/CT)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 1
- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only
- Ability to complete questionnaire(s) by themselves or with assistance
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the active
monitoring phase of the study)
- Willing to provide blood samples for correlative research purposes, including
anonymous shipment of samples to for NavDx testing
Exclusion Criteria:
- Any of the following:
- 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
- Immunocompromised patients and patients known to be human immunodeficiency virus
(HIV)+
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements
- Receiving any other investigational agent which would be considered as a treatment
for the primary neoplasm
- Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Nonmelanotic
skin cancer or carcinoma-in-situ of the cervix, or prostate or localized
endometrioid endometrial cancer. NOTE: If there is a history or prior malignancy,
they must not be receiving other specific treatment for their cancer
- Prior history of radiation therapy to the affected site
- Prior systemic chemotherapy in the last 5 years
- Contraindication to radiation therapy as determined by the treating team
- History of allergic reaction to docetaxel
- Receiving any medications or substances which in the opinion of the investigators
would interfere with treatment. Examples could include strong inhibitors of
cytochrome P450 3A4 (CYP3A4) at oncologist discretion
- Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the
investigator, preclude the use of cisplatin chemotherapy
- cT4 primary tumor
- NOTE: Patients with no intermediate risk factors after surgery, low risk
patients, as defined by T1, T2, tumors with lymph node less than 3cm, no
intermediate or high risk factors such as lymphatic invasion (LVSI), ENE,
perineural invasion (PNI), positive margin, will go off study and be observed
per current clinical standard of care
- Patients found to have HPV non 16 type, or HPV detectability in blood less than
<20tumor tissue modified viral (TTMV) will not be candidates for de-escalation
in Groups 1 and 2 and will be treated in Group 3. They will receive 60 Gy +/-
cisplatin or acceptable alternate regimen when drug shortages of cisplatin
exist. If treated primarily with chemoradiation (chemoRT) (Group 4), these
patients will not be candidates for de-escalation if TTMV is < 50 TTMV but can
remain on study receiving 70 Gy with all corresponding correlative studies
applying
- Patients with unknown (radiologic/clinically occult) primaries but p16+ or HPV+
neck adenopathy can be registered to go on study. Should after primary
resection, no primary tumor be identified, the patient will go off study and be
treated per institutional standard of care
- All treatment primarily, including surgery and chemotherapy will be performed
at the enrolling institution
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Contact backup:
Last name:
Shelby Watkin
Phone:
480-342-2000
Investigator:
Last name:
Samir H. Patel, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Contact backup:
Last name:
Caroline Pamboukas
Phone:
904-953-2791
Investigator:
Last name:
Adam L. Holtzman, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
David M. Routman, M.D.
Email:
Principal Investigator
Start date:
February 21, 2023
Completion date:
August 1, 2029
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05541016
https://www.mayo.edu/research/clinical-trials
