Phase II Trial of Neoadjuvant Chemotherapy for HPV-Associated Squamous Cell Carcinoma of the Oropharynx Followed by Reduced Dose Radiotherapy/Chemoradiotherapy for Responders or Standard Dose Chemoradiotherapy for Non-Responders
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Response (CR+PR) Status at 3 Months Post-therapy
研究概览
简要总结
This study looks at the use of three cycles of chemotherapy given prior to radiation therapy in patients with cancer of the oral cavity and evidence of prior exposure to Human Papilloma Virus (HPV). Patients with cancer of the oral cavity who have evidence of exposure to HPV have a better prognosis than those who do not have such evidence of exposure to HPV. The main hypothesis of this study is that using three cycles of chemotherapy prior to embarking on radiation therapy will allow the use of reduced doses of radiation therapy and, therefore, less radiation induced side-effects. The primary objective is to determine the activity of this pre-radiation chemotherapy strategy along with reduced dose levels of radiation with or without chemotherapy during the radiation phase. The effectiveness of the strategy will be assessed at three months following the completion of the radiation therapy phase and also at two years following completion of the radiation therapy.
详细描述
Induction Chemotherapy TPF induction chemotherapy will be administered as published from the TAX 323 phase III trial. Specifically, each cycle will consist of docetaxel at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, followed by cisplatin at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, and fluorouracil at a dose of 750 mg per square meter per day, administered by continuous infusion on days 1 to 5. Induction chemotherapy will be given every 3 weeks for three cycles, unless there is distant disease progression, unacceptable toxic effects, or withdrawal of consent by the patient. All patients will be required to have a continuous venous access device such as a PICC line or Infusaport type device. This is standard of care for continuous infusion fluorouracil. Response assessment by examination, contrast-enhanced CT imaging and whole body PET-CT will be performed after the third treatment cycle. Radiotherapy or chemoradiotherapy will commence within 3-4 weeks from the conclusion of the induction program.
Selection for Radiation Alone vs. Chemoradiotherapy For CR/PR patients with CR at primary site following induction chemotherapy, locoregional therapy will be risk-adjusted according to baseline tumor stage/characteristics. Local therapy will be 1) radiotherapy as a single modality for Tx (T1-2), T0-1 or exophytic T2, N0-2a disease, or will be 2) concomitant chemoradiotherapy for Tx (T3), endophytic T2, T3, N2b-c disease. Patients with PR at primary site will receive concurrent chemotherapy and reduced dose radiation.
All SD/PD patients will receive concurrent chemotherapy and full dose radiation. Patients catalogued with disease progression on the basis of new distant metastatic disease spread (DM) during induction chemotherapy will be taken off protocol for consideration of palliative therapy.
Concurrent Chemotherapy Concurrent chemotherapy will consist of cisplatin given at 35 mg/m2 weekly for six cycles OR carboplatin given at AUC 1.5 weekly for six cycles. Concurrent chemotherapy will start during the first week of radiation treatment. Selection of either schedule will be left to the discretion of the attending medical oncologist. Concurrent chemotherapy will be held for a platelet count of <100,000 or an absolute neutrophil count of < 1000 per cubic mm.
IMRT doses Primary Target (residual gross disease): 66 Gy called CTV1 (2.2 Gy/fraction in 30 fractions).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Tumor tissue available from primary or nodal metastasis for histological analysis.
- •High p16 tumor expression by IHC, or indeterminate p16 expression by IHC and definitively positive detection of high-risk HPV infection by ISH.
- •T-stage = T1-3 or post-tonsillectomy Tx (T1-3).
- •N-stage = N1-2 or Nx (N1-2).
- •Biopsy-confirmed oropharyngeal primary site.
- •Histology = squamous cell carcinoma, basaloid-squamous carcinoma, nasopharyngeal-type squamous carcinoma, adenosquamous carcinoma, or papillary squamous carcinoma.
- •Age > 17 years old.
- •Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC at least 1500 cells/mm3 and platelet count at least 100,000 cells/mm3); adequate hepatic function with bilirubin less than 1.5x ULN (excluding Gilbert's disease); SGOT, SGPT and alkaline phosphatase must be within the normal range to be eligible for study.
- •Creatinine clearance at least 70 ml/min determined by 24 hour collection or nomogram: CrCl male = (140 - age) x (wt in kg)/serum Cr x 72; CrCl female = 0.85 x (CrCl male).
- •Patients must have an untransfused hemoglobin of at least 9.0 grams/dL.
- •Patients should have no serious acute or chronic co-morbid condition, or acute infection, which in the judgment of the attending physician would affect administration of the induction chemotherapy regimens.
- •Patients must sign a study-specific informed consent form.
- •All of the above lab criteria must be verified within 28days of registration.
排除标准
- •Low p16 expressing tumor by IHC, or indeterminate p16 expression by IHC and negative or weak detection of high-risk HPV infection by ISH.
- •TxNx without residual measurable disease, T4, or N3 disease.
- •Significant cigarette smoking history, defined as >10 pack-years total lifetime exposure. Pack years is calculated as # packs smoked per day x # years smoking.
- •Histology other than squamous cell carcinoma.
- •Proven distant metastases (below the clavicle) by clinical or radiographic measures.
- •Karnofsky performance status < 80 or ECOG >
- •Prior chemotherapy, within the previous 3 years.
- •Prior radiotherapy to the head and neck.
- •Initial surgical resection rendering the patient clinically and radiologically disease free.
- •Simultaneous primary invasive cancers, excluding superficial non-melanoma skin cancers.
- •Patients with a history of another malignancy (excluding non melanoma skin cancers, and cancers treated > 3 years prior for which patient remains continuously disease free).
- •Men and women of childbearing potential (WOCBP) unwilling to consent to using effective contraception while on treatment and for at least 3 months thereafter. Note: WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for 3 months after the study in such a manner that the risk of pregnancy is minimized.
研究组 & 干预措施
Chemotherapy non-responders
Patients treated with three cycles neoadjuvant chemotherapy who do not exhibit response to chemotherapy are then allocated to recieve standard dose and schedule radiotherapy.
干预措施: chemotherapy (Drug)
Chemotherapy non-responders
Patients treated with three cycles neoadjuvant chemotherapy who do not exhibit response to chemotherapy are then allocated to recieve standard dose and schedule radiotherapy.
干预措施: radiotherapy (Radiation)
Chemotherapy responders
Patients who respond to chemotherapy are treated with reduced dose radiotherapy.
干预措施: chemotherapy (Drug)
Chemotherapy responders
Patients who respond to chemotherapy are treated with reduced dose radiotherapy.
干预措施: Reduced dose radiotherapy (Radiation)
结局指标
主要结局
Response (CR+PR) Status at 3 Months Post-therapy
时间窗: 3 months following completion of radiation phase
The 3-month response rate will be estimated using standard methods for estimating proportions and their 95% one-sided confidence intervals (CIs). Comparison to the historical control data will be carried out using a chi-square test for comparing proportions (or a Fisher exact test if an expected cell frequency in the 2x2 table is less than 5). Zero (0) participants analyzed
次要结局
- Progression-free Survival at 2 Years(At two years following completion of radiation phase)
- Assess Overall Survival at 2 Years.(At two years following completion of radiation phase)
- Assess Locoregional Disease Control at 2 Years(At two years following completion of radiation phase)
- Assess Distant Disease Control at 2 Years.(At two years following completion of radiation phase)
- Identify Additional Toxicity of Treatment(During therapy and up to 5 years following completion of treatment)
- To Define Objective Tumor Response Rates to Induction Chemotherapy and to Subsequent Radiation-based Treatment.(Three months following completion of radiation therapy phase.)
- Assessment of Quality of Life Outcomes(Baseline, during therapy and up to two years following completion of radiation phase)