Low-Dose Radiation Therapy with Standard Chemotherapy for the Treatment of Patients with Human Papillomavirus-Associated Stage I-IVa Oropharyngeal Cancer
This phase II trial evaluates whether lower-dose radiation therapy in combination with standard of care chemotherapy works to treat and reduce side effects in patients with human papillomavirus positive, stage I-IVa oropharyngeal cancer. Radiation therapy such as intensity-modulated radiation therapy, volume modulated arc therapy, and proton beam radiation therapy use high energy rays or protons to kill tumor cells and shrink tumors. Chemotherapy drugs such as cisplatin, carboplatin, and fluorouracil work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Inclusion Criteria
- Pathologically (histologically or cytologically) proven diagnosis of HPV-associated squamous cell carcinoma of the oropharynx (tonsil, the base of the tongue, or oropharyngeal walls) from biopsy, surgical resection, or excisional biopsy regardless of margin status. * Squamous cell carcinoma of the neck of an unknown primary is allowed with an excision biopsy of a lymph node (or core biopsy) or consent from the principal investigator (PI) or co-PI * Patient must have an excisional biopsy or core biopsy done in order to be on protocol
- Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations
- Oropharyngeal Carcinoma (American Joint Committee on Cancer [AJCC], 7th ed.) without evidence of distant metastasis based on fludeoxyglucose (FDG) PET/CT
- CT or MRI of the neck with and without contrast * Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or Karnofsky performance status (KPS) >= 50
- Age >= 18 (Patients over 70 years [yrs] will be able to enroll in Cohort B only)
- Blood count (white blood cells [WBC]) >= 2 K/mcL (within 30 days prior to registration)
- Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (within 30 days prior to registration)
- Platelets >= 100,000 cells/mm^3 (within 30 days prior to registration)
- Hemoglobin >= 8.0 g/dl; Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 8.0 g/dl is acceptable (within 30 days prior to registration)
- Serum creatinine =< 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula (within 30 days prior to registration); Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Paclitaxel can be substituted with Abraxane
- Bilirubin =< 2 mg/dl (within 30 days prior to registration)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x the upper limit of normal (within 30 days prior to registration) * Note: Exceptions can be made with principal investigator (PI) and/or Co-PI approval for patients to enroll on trial with a higher bilirubin level such as Gilbert’s Syndrome
- Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Paclitaxel can be substituted with Abraxane. Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
- The subject must provide study-specific informed consent prior to study entry. Subject able to undergo MRI scans except for major medical contraindications like presence of a pacemaker or approved by the PI or the CO-PI that the subject does not need to undergo MRI scans
Exclusion Criteria
- Subjects with prior head and neck radiation therapy
- Subjects with simultaneous primary cancers outside of the oropharynx * Note: Exceptions can be made for patients with simultaneous primaries outside the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- Severe, active co-morbidity defined as follows (exceptions can be made if approved by the PI and/or co-PI): * 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 registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Additional locations may be listed on ClinicalTrials.gov for NCT05491512.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
PRIMARY OBJECTIVE:
I. To demonstrate that the 2-year locoregional control for subjects with human papillomavirus (HPV) positive oropharyngeal carcinoma treated with a personalized radiation treatment plan is acceptable when compared to subjects treated with the current standard chemoradiation at 70Gy.
SECONDARY OBJECTIVES:
I. To assess the 2-year local, regional, and distant metastasis progression-free rates, progression-free survival, and overall survival rates.
II. To assess the pattern of failure (i.e., in-field vs out-of-field of gross nodal disease) for patients who receive radiation to the primary tumor site and gross nodal disease.
III. To assess the local progression-free rate for T3 and T4 patients.
IV. To assess the acute and late toxicities of treatment of all patients in their respective cohorts.
V. To assess the subject-reported outcomes at baseline, end of radiation, 4 months (+/-2 weeks), 1 year (+/-2 months), and 2 years (+/-2 months) after the end of radiation.
VI. To examine the association between disease outcomes (i.e., locoregional recurrence, distant metastasis, disease progression, and overall survival) and the following factors: pre-treatment, week 2, and week 4 of chemoradiation dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging (MRI).
EXPLORATORY OBJECTIVES:
I. To examine the T cell repertoire pre, 1, and 2 weeks into chemoradiation, 1 year post-chemoradiation.
II. To examine the association between disease outcomes by examining tissue biomarkers on pre-treatment and post-week 2 (W2) 18F-fluoromisonidazole (18F-FMISO) tissue specimens using whole exome sequencing assessing mutational signatures and mutations including PI3KCA, TP53, FAT1, NOTCH1, PTEN; DNA repair genes like ATM, ATR, DNA PK, CDKN2A; RNA sequencing examining expression based signatures (including subtypes such as atypical, mesenchymal, and immune cell subset de-convolution) and viral expression; RAD51 and gamma H2AX staining; HPV subtyping specifically 16, 18, 31, 33); PDL1 staining.
OUTLINE: Patients are assigned to 1 of 4 cohorts.
COHORT A: Patients undergo intensity-modulated radiation therapy (IMRT), volume-modulated arc therapy (VMAT), or proton beam radiation therapy (PBRT) 5 days per week for 3 weeks. Patients also receive cisplatin intravenously (IV) on day 1 or days 1-2 of cycles 1 (week1) and cycle 2 (week 4). If cisplatin cannot be given, patients receive carboplatin IV and fluorouracil (5-FU) IV daily for 4 days during cycles 1 and 2. After 5-10 chemoradiation treatment days, patients receive 18F-fluoromisonidazole (FISMO) IV and undergo positron emission tomography (PET)/computed tomography (CT) over 10 minutes. Patients also undergo FDG PET/CT and MRI during screening and on study and blood sample collection throughout the trial. Patients may optionally undergo a biopsy on study.
COHORT B: Patients undergo IMRT, VMAT, or PBRT 5 days per week for 3 weeks. Patients also receive carboplatin IV and paclitaxel IV weekly for 5 weeks. Paclitaxel may be substituted for nab-paclitaxel. After 5-10 chemoradiation treatment days, patients receive FISMO IV and undergo PET/CT over 10 minutes. Patients also undergo FDG PET/CT and MRI during screening and on study and blood sample collection throughout the trial. Patients may optionally undergo a biopsy on study.
COHORT C: Patients undergo IMRT, VMAT, or PBRT 5 days per week for 3 weeks. Patients also receive paclitaxel IV and carboplatin IV, with or without cetuximab IV weekly for 6 weeks. Paclitaxel may be substituted for nab-paclitaxel. Patients also receive FISMO IV and undergo PET/CT over 10 minutes during screening and after 5-10 chemoradiation treatment days. Patients also undergo FDG PET/CT and MRI during screening and on study and blood sample collection throughout the trial. Patients may optionally undergo a biopsy on study.
COHORT D: Patients undergo IMRT, VMAT, or PBRT 5 days per week for 3 weeks. Patients also receive cisplatin or carboplatin/5-FU as in Cohort A, or carboplatin and paclitaxel as in Cohort B. Paclitaxel may be substituted for nab-paclitaxel. After 5-10 chemoradiation treatment days, patients receive FISMO IV and undergo PET/CT over 10 minutes. Patients also undergo FDG PET/CT and MRI during screening and on study and blood sample collection throughout the trial. Patients may optionally undergo a biopsy on study.
After completion of the study treatment, patients are followed up at 4 months and years 1 and 2.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorNancy Y. Lee
- Primary ID22-215
- Secondary IDsNCI-2022-06671
- ClinicalTrials.gov IDNCT05491512