Oropharyngeal Carcinoma
Conditions
Keywords
Human Papilloma Virus Associated, Chemoradiation, T3-4/N0-2c or any N3, 25-040
Brief summary
The researchers are doing this study is to find out if lower doses (given in fewer treatments over a shorter period of time) of radiation therapy in combination with standard-of-care chemotherapy is an effective treatment for people with Human Papilloma Virus (HPV)-positive throat cancer and works as well as the standard doses of radiation therapy in combination with standard-of-care chemotherapy. The chemotherapy drugs used in combination with radiation therapy in this study include cisplatin, carboplatin, and 5-fluorouracil (5-FU).
Interventions
DIAGNOSTIC_TEST18F-FMISO PET/CT Scan
The 18F-FMISO PET/CT Scan Protocol consists first of an IV bolus injection of approximately 5-10 mCi of the radiotracer. Subjects will undergo 18F-FMISO scan (only 1 injection) occurs at 8-10 treatment days\* into chemoradiation. Each patient will have a baseline staging FDG PET scan which is used to localize the tumor at the primary site and all suspicious cervical neck nodes (\> 1 cm in short axis diameter with focal abnormal increased FDG avidity). These lesions are then assessed on the respective 18F-FMISO PET/CT.
COMBINATION_PRODUCTChemoradiation
Patients will start with induction chemotherapy of carboplatin, paclitaxel and cetuximab for 6 weeks and when downstaged to T1-2 and \< N3, the patient is eligible to receive concurrent chemoradiation per protocol. All subjects will undergo radiation treatments (IMRT and/or proton therapy). A total radiation therapy of 30Gy will be delivered to the oropharynx and neck at 2Gy per fraction per day over 15 days for patients who exhibited no evidence of hypoxia on the intra-treatment 18F-FMISO PET/CT. Concurrent chemotherapy (2 cycles) will be given. After completion of chemotherapy and radiation therapy, a 4 month (+/-4 weeks)
OTHERQuestionnaires
EQ-5D-5L, MDADI-HN, COST-FACIT
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This non-randomized phase II study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from biopsy, surgical resection or excisional biopsy regardless of margin status. 1. Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI. Patient must have excisional biopsy or core biopsy done in order to be on protocol. Note: Evidence of HPV associated oropharyngeal cancer from either the primary tumor site or from a lymph node. A patient is HPV positive when he or she tests positive having tested positive for both p16 expression (70% nuclear and cytoplasm expression; Ventana Medical Systems) and mRNA HPV in situ hybridization. * Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations. * T3-4/N0-2c or any N3 regardless of Tstage (AJCC 7th Edition) HPV+ OPC\* or HPV associated squamous cell carcinoma with nodal metastasis (es) but unknown primary sites without evidence of distant metastasis based on FDG PET/CT. * CT Neck with contrast 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. * ECOG Performance Status of 0-2 or KPS ≥ 70 * Age ≥ 18 * Adequate hematologic function within 30 days prior to registration, defined as follows: 1. White Blood Count (WBC) ≥ 2 K/mcL 2. Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3 3. Platelets ≥ 100,000 cells/mm\^3 4. Hemoglobin ≥ 8.0 g/dl Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable * Adequate renal function within 30 days prior to registration, defined as follows: a. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula CCr male = \[(140 - age) x (wt in kg)\] \[(Serum Cr mg/dl) x (72)\] CCr female = 0.85 x (CrCl male) Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel * Adequate hepatic function within 30 days prior to registration, defined as follows: 1. Bilirubin ≤ 2 mg/dl 2. AST or ALT ≤ 3 x the upper limit of normal Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential * One cycle of induction chemo therapy is allowed prior to registration based on clinical needs. * 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 if determined by the PI/Co-PI the patient can proceed with protocol activities. 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) 1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months 2. Transmural myocardial infarction within the last 6 months 3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration 4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration 5. Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional control | 2 years | Researchers will test the null hypothesis H0: P=78% vs the alternative hypothesis H1:P=91%, where P represents the 2-year locoregional control (LRC). We will use the Kaplan-Meier method to estimate the LRC rate at 2 years and construct a 0.975 1-sided confidence interval in order to achieve a test size alpha = 0.05 (this is based on a finite-sample correction using 100,000 simulations). |
Countries
United States
Contacts
CONTACTNancy Lee, MD
CONTACTNadeem Riaz, MD
PRINCIPAL_INVESTIGATORNancy Lee, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed