Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Advanced Stage Human Papilloma Virus Associated Oropharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 14
- 主要终点
- Locoregional control
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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
- •Adequate hematologic function within 30 days prior to registration, defined as follows:
- •White Blood Count (WBC) ≥ 2 K/mcL
- •Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3
- •Platelets ≥ 100,000 cells/mm^3
- •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:
- •Bilirubin ≤ 2 mg/dl
- •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
排除标准
- •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)
- •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
研究组 & 干预措施
Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer
Subjects will first undergo 6 weeks of standard induction chemotherapy and if downstaged to T1-2 and <N3 and also have no evidence of hypoxia will undergo a major de-escalated radiation therapy to 30Gy concurrent with standard chemotherapy. Hypoxia status is determined by the absence of hypoxia uptake on Fluorine-18-Labeled Fluoro-Misonidazole (18F-FMISO) PET/CT imaging (8-10 treatment days after start of chemoradiation), which has an FDA approved IND for use in humans . If the 18F-FMISO PET is negative for hypoxia, the patient will receive 30Gy concurrent with 2 cycles of chemotherapy. If the 18F-FMISO PET is positive for hypoxia, the patient will receive standard of care 70Gy concurrent with 3 cycles of chemotherapy. An optional 18F-FMISO scan will also be offered at baseline.
干预措施: 18F-FMISO PET/CT Scan (Diagnostic Test)
Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer
Subjects will first undergo 6 weeks of standard induction chemotherapy and if downstaged to T1-2 and <N3 and also have no evidence of hypoxia will undergo a major de-escalated radiation therapy to 30Gy concurrent with standard chemotherapy. Hypoxia status is determined by the absence of hypoxia uptake on Fluorine-18-Labeled Fluoro-Misonidazole (18F-FMISO) PET/CT imaging (8-10 treatment days after start of chemoradiation), which has an FDA approved IND for use in humans . If the 18F-FMISO PET is negative for hypoxia, the patient will receive 30Gy concurrent with 2 cycles of chemotherapy. If the 18F-FMISO PET is positive for hypoxia, the patient will receive standard of care 70Gy concurrent with 3 cycles of chemotherapy. An optional 18F-FMISO scan will also be offered at baseline.
干预措施: Chemoradiation (Combination Product)
Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer
Subjects will first undergo 6 weeks of standard induction chemotherapy and if downstaged to T1-2 and <N3 and also have no evidence of hypoxia will undergo a major de-escalated radiation therapy to 30Gy concurrent with standard chemotherapy. Hypoxia status is determined by the absence of hypoxia uptake on Fluorine-18-Labeled Fluoro-Misonidazole (18F-FMISO) PET/CT imaging (8-10 treatment days after start of chemoradiation), which has an FDA approved IND for use in humans . If the 18F-FMISO PET is negative for hypoxia, the patient will receive 30Gy concurrent with 2 cycles of chemotherapy. If the 18F-FMISO PET is positive for hypoxia, the patient will receive standard of care 70Gy concurrent with 3 cycles of chemotherapy. An optional 18F-FMISO scan will also be offered at baseline.
干预措施: Questionnaires (Other)
结局指标
主要结局
Locoregional control
时间窗: 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).
次要结局
未报告次要终点