Trial Title:
Using CircuLating Tumor DNA to Risk Adapt Post-Operative Therapy for HPV-associated Oropharyngeal Cancer
NCT ID:
NCT06445114
Condition:
Oropharyngeal Cancer
Carcinoma
Conditions: Official terms:
Oropharyngeal Neoplasms
Cisplatin
Conditions: Keywords:
Transoral Robotic Surgery (TORS)
pT0 tumors (unknown primary)
p16
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Prospective single arm multicenter clinical trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Low risk pathology with post-op HPV DNA (-): cisplatin-based chemoradiation with 30 Gy in
15 fractions and 3 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, and 15 of
radiation.
Low risk pathology with post-op HPV DNA (+): cisplatin-based chemoradiation with 40 Gy in
20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of
radiation.
High risk pathology with post-op HPV DNA (-), excluding patients with both 5 LN+ and ENE+
or pre-op HPV DNA≤12 copies/mL: cisplatin-based radiation with 40 Gy in 20 fractions and
4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation.
High risk pathology with post-op HPV DNA (+) OR pre-op HPV DNA≤12 copies/mL OR both 5 or
more LN+ and ENE+: cisplatin-based radiation with 50 Gy in 25 fractions with 5 cycles of
weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, 22, and 29 of radiation.
Arm group label:
Single Arm
Other name:
Chemoradiation
Summary:
This is a single institution phase II study that will enroll patients with T0-3N0-2
p16-positive oropharyngeal squamous cell carcinoma (OSCC) undergoing resection of all
gross visible disease at the primary site and in the lymph nodes.
Detailed description:
All eligible patients will be treated with a de-intensified cisplatin-based
chemoradiation regimen after undergoing transoral robotic surgery. Enrolled patients will
be risk-assessed and assigned to specific regimens based on a combination of their
post-operative cTTMV-HPV DNA, as determined by results from NavDx kits by Naveris, and
pathologic features. All patients will receive a dose of 40 mg/m2 IV weekly concurrently
with radiation therapy. Patients ineligible to receive cisplatin at this dose will
undergo modified sydtemic therapy. Patients will recieve concurrent radiation in a dose
of 30 Gy in 15 fractions to the primary tumor bed, ipsilateral neck +/- contralateral
neck. Based on risk-stratification, some patients will receive a sequential boost of 10
Gy over 5 fractions or 20 Gy over 10 fractions.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- AJCC 8th edition T0-3N0-2 p16-positive oropharyngeal (tonsil, base of tongue,
glossotonsillar sulcus, soft palate, oropharyngeal wall) squamous cell carcinoma or
squamous cell carcinoma of unknown primary involving the cervical lymph nodes.
Cytologic diagnosis from a cervical lymph node is sufficient for diagnosis in the
presence of clinical evidence of a primary tumor in the oropharynx.
- For patients with pT0 tumors (unknown primary), there must be at least one
metastatic lymph node present in cervical level II.
- p16 is strongly positive by immunohistochemistry or high-risk HPV is detected by
in-situ hybridization.
- Have undergone or will undergo gross total resection of all known disease in the
head and neck via transoral robotic surgery. For patients with clinical unknown
primary tumors, a patient must undergo both ipsilateral tonsillectomy and base of
tongue resection unless the primary is identified clinically or pathologically at
the time of surgery. If the primary is identified, then only resection of the
primary site is required. If the primary tumor is resected with negative margins
with a non-robotic surgery, such as a diagnostic tonsillectomy, this is considered
acceptable and further robotic surgery is not necessary.
- Have undergone or will undergo neck dissection.
- Have at least one of the following after surgery:
- Pathologic stage T3
- 2 or more positive lymph nodes
- At least one lymph node >3cm
- Contralateral lymph node involvement
- Lymphovascular invasion
- Perineural invasion
- Extranodal extension
- Close/positive margins: Close margins are considered ≤3mm from the peripheral
margins and ≤1mm from the deep margin on the en bloc specimen, unless the area
of close margin is re-resected and without carcinoma.
- Patients consented preoperatively are required to have detectable cTTMV-HPV DNA
based on pre-operative NavDx testing. For patients consented post-operatively, NavDx
testing should be performed on the tumor tissue to ensure detectable HPV DNA and for
HPV subtyping.
- Age ≥ 18 years old
- ECOG performance status 0 or 2 within 56 days of start of chemoradiation.
- Women of childbearing potential require a negative serum or urine pregnancy test
within 28 days prior to start of chemoradiation.
- Written informed consent obtained from subject and ability for subject to comply
with the requirements of the study.
- Adequate hematologic and renal function within 56 days of start of chemoradiation,
defined as:
- Hemoglobin ≥ 9.0 g/dL
- Platelets ≥ 100, 000 cells/mm3
- ANC ≥ 1.5 X 109/L
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase/alanine aminotransferase ≤ 3.0 x upper limit of
normal (ULN)
- Serum creatinine ≤1.5 x upper limit of normal (ULN) OR a calculated creatinine
clearance ≥50 mL/min estimated using the following Cockcroft-Gault equation
Exclusion Criteria:
- AJCC 8th edition pT4 or cN3 disease.
- Radiologic or clinical evidence of distant metastasis.
- Recurrent disease.
- Inability to achieve gross total resection at time of surgery.
- Greater than 56 days (8 weeks) after surgical resection of the primary site.
- Prior radiation to the head and neck > 30 Gy.
- Prior active invasive (not in situ) malignancy within the prior 2 years, excluding
cutaneous basal cell or squamous cell carcinoma, low or intermediate risk prostate
cancer, papillary thyroid cancer, stage T1aN0 kidney cancer, low-grade T1-2N0
salivary cancer, AJCC 8th edition stage I-II breast cancer, well-differentiated
neuroendocrine tumors (e.g., carcinoid tumors), low grade non-Hodgkin lymphoma, or
Stage 0, I, and III cutaneous melanomas. Patients with synchronous or multifocal
oropharyngeal cancers are not excluded, as long as at least one of these tumors meet
inclusion criteria for the trial.
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization
within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of enrollment
- Hepatic insufficiency resulting in clinical jaundice and/or known coagulation
defects
- Moderate to severe hearing loss.
- Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma)
requiring immunosuppression.
- Pregnant or breast-feeding women.
- Prior allergic reaction to cisplatin.
- Live vaccines within 30 days prior to the first dose of chemoradiation. Examples of
live vaccines include, but are not limited to, the following: measles, mumps,
rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral vaccine). Season
influenza vaccines for injection are generally killed virus vaccines and are
allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated
vaccines and are not allowed.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cedars-Sinai Cancer at Beverly Hills (THO)
Address:
City:
Beverly Hills
Zip:
90211
Country:
United States
Contact:
Last name:
Clinical Trial Recruitment Navigator
Investigator:
Last name:
Kevin Scher, MD
Email:
Sub-Investigator
Investigator:
Last name:
David Hoffman, MD
Email:
Sub-Investigator
Investigator:
Last name:
Kamalesh Sankhala, MD
Email:
Sub-Investigator
Investigator:
Last name:
Leland Green, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jeremy Lorber, MD
Email:
Sub-Investigator
Facility:
Name:
Cedars Sinai Medical Center
Address:
City:
Los Angeles
Zip:
90048
Country:
United States
Contact:
Last name:
Zachary S Zumsteg, MD
Phone:
310-248-8375
Email:
zachary.zumsteg@cshs.org
Investigator:
Last name:
Allen Ho, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jon Mallen-St. Clair, MD
Email:
Sub-Investigator
Investigator:
Last name:
Evan Walgama, MD
Email:
Sub-Investigator
Investigator:
Last name:
Alain Mita, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jun Gong, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ronald Natale, MD
Email:
Sub-Investigator
Investigator:
Last name:
Stephen Shiao, MD
Email:
Sub-Investigator
Investigator:
Last name:
Julie Jang, MD
Email:
Sub-Investigator
Investigator:
Last name:
Zachary S Zumsteg, MD
Email:
Principal Investigator
Facility:
Name:
CS Cancer at Valley Oncology Medical Group
Address:
City:
Tarzana
Zip:
91356
Country:
United States
Contact:
Last name:
Vanessa Vasco
Email:
Vanessa.Vasco@cshs.org
Investigator:
Last name:
Benjamin L King, MD
Email:
Sub-Investigator
Investigator:
Last name:
Robert S Reznik, MD
Email:
Sub-Investigator
Investigator:
Last name:
Natasha Banerjee, MD
Email:
Sub-Investigator
Investigator:
Last name:
Johnny K Chang, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ryan Ponec, MD
Email:
Sub-Investigator
Investigator:
Last name:
Anirban Balmanoukian, MD
Email:
Sub-Investigator
Facility:
Name:
CS Cancer at the Hunt Cancer Center
Address:
City:
Torrance
Zip:
90505
Country:
United States
Contact:
Last name:
Sarah Valdez
Phone:
310-750-3300
Phone ext:
73422
Email:
Sarah.Valdez@tmphysicians.com
Investigator:
Last name:
Hugo Hool, MD
Email:
Sub-Investigator
Investigator:
Last name:
Vanessa Dickey, MD
Email:
Sub-Investigator
Investigator:
Last name:
David Chan, MD
Email:
Sub-Investigator
Investigator:
Last name:
Syed Jilani, MD
Email:
Sub-Investigator
Investigator:
Last name:
Thomas Lowe, MD
Email:
Sub-Investigator
Investigator:
Last name:
Swati Sikaria, MD
Email:
Sub-Investigator
Investigator:
Last name:
Andrew Horodner, MD
Email:
Sub-Investigator
Investigator:
Last name:
Bryan Chang, MD
Email:
Sub-Investigator
Investigator:
Last name:
Thyra Endicott, MD
Email:
Sub-Investigator
Investigator:
Last name:
Andrew Schumacher, MD
Email:
Sub-Investigator
Investigator:
Last name:
Usama Mahmood, MD
Email:
Sub-Investigator
Investigator:
Last name:
Rebecca Philipson, MD
Email:
Sub-Investigator
Start date:
July 2024
Completion date:
July 2031
Lead sponsor:
Agency:
Zachary Zumsteg
Agency class:
Other
Source:
Cedars-Sinai Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06445114
