Phase II Randomized Trial of Neoadjuvant Chemotherapy Followed by Surgery and Post-Operative Radiation Versus Surgery and Post-Operative Radiation for Organ Preservation of T3 and T4a (and Selected T4b) Nasal and Paranasal Sinus Squamous Cell Carcinoma (NPNSCC)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 82
- 试验地点
- 423
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase II trial studies how well chemotherapy before surgery and radiation therapy works compared to surgery and radiation therapy alone in treating patients with nasal and paranasal sinus cancer that can be removed by surgery. Chemotherapy drugs, such as docetaxel, cisplatin, and carboplatin, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy before surgery and radiation therapy may make the tumor smaller and reduce the amount of normal tissue that needs to be removed and treated with radiation.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the structure preservation rate for patients with locally advanced resectable nasal and paranasal sinus squamous cell carcinoma (NPNSCC) with or without neoadjuvant therapy; all patients will undergo surgical resection and postoperative standard care.
II. Evaluate overall survival (OS) for patients with locally advanced resectable NPNSCC with or without neoadjuvant therapy followed by surgical resection and postoperative standard care.
SECONDARY OBJECTIVES:
I. Evaluate progression-free survival (PFS) for this patient population. II. Examine the rate of structure preservation for the orbit (freedom from orbital exenteration).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients must be >= 18 years of age
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients must have a general physical condition compatible with the proposed chemotherapy and surgery
- •Patients must have stage T3 or T4a, histologically-confirmed NPNSCC requiring orbital or skull base resection: (Some patients with T4b disease deemed resectable by the treating surgeon can be included provided they fulfill all other eligibility criteria without involvement of the cavernous sinus
- •Patients with T4b who have the following characteristics leading to a T4b definition but who in the opinion of the treating surgeon can have resectable disease can be included provided they fulfill all other eligibility criteria and provided they have one of the following presentations:
- •Invasion of orbital apex without involvement of the cavernous sinus
- •Dura invasion depending on extent of involvement and if total resection is deemed feasible.
- •Brain/middle cranial fossa invasion depending on extent of involvement if total resection is deemed feasible.
- •Nasopharynx invasion if very limited
- •Clivus invasion if very limited. (Surgeons are encouraged to consult with the protocol surgical chair for these particular cases). Stages T3 and T4a and selected T4b disease will be included regardless of nodal status (N0 or N1-3), provided that surgical therapy would require orbital or skull base resection. The surgical oncologist in each institution will determine the need for resection of the orbit OR base of skull at baseline for patients on both Arms A and B and following neoadjuvant chemotherapy for patients on Arm B using the score sheet provided at the end of the protocol.
- •Resection of skull base will be deemed necessary according to skull base bone erosion by computed tomography (CT) or marrow involvement by magnetic resonance imaging (MRI) is noted; for any disease abutting the skull base
- •Resection of orbital contents will be deemed necessary according to skull base society guidelines, based on involvement of periorbital fat documented by MRI imaging
- •Patients must be deemed surgically resectable by the surgical teams at each institution and must have a determination of degree of anticipated structure preservation of orbit and skull base; this needs to be determined prior to randomization
- •Patients must not have received previous irradiation for head and neck tumor, skull base, or brain tumors
- •Absolute neutrophil count (ANC) > 1500/mm^3 (=< 2 weeks prior to randomization)
- •Hemoglobin (Hgb) > 8.0 g/dL (=< 2 weeks prior to randomization)
- •Platelet count > 100,000/mm^3 (=< 2 weeks prior to randomization)
- •For patients receiving cisplatin, creatinine clearance must be > 60 ml/min (=< 2 weeks prior to randomization); creatinine clearance may be measured or calculated; if calculating, creatinine clearance, use the Cockcroft-Gault formula
- •Total bilirubin within 1.5 x the upper limit of normal (ULN) (must be obtained =< 2 weeks prior to randomization)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within 1.5 x ULN allowing for eligibility (must be obtained < 2 weeks prior to randomization)
- •Alkaline phosphatase must be within 1.5 x ULN allowing for eligibility (must be obtained < 2 weeks prior to randomization)
- •Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated
- •Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the chemotherapy and radiation being used; in addition, complications from pregnancy may interfere with the ability of patients to have an uninterrupted therapy
- •All patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- •A patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achived menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- •Patient must not be expected conceive or father children by using an accepted and effective method(s) of contraception or by abstain from sexual intercourse for the duration of their participation in the study
- •Patient must have measurable disease; MRI and/or PET/CT scans need to be performed within 2 weeks prior to randomization
排除标准
- •Patients may not be receiving investigational agents at time of randomization, or at any time while on study and during the 4 weeks preceding randomization
- •Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel and/or both platinum-based chemotherapy agents are ineligible; patient must be able to receive at least one of the two proposed chemotherapy regimens
- •Patients with evidence of distant metastases or leptomeningeal disease (LMD) are ineligbile
- •Patients with uncontrolled inter-current illnesses which in the opinion of the investigator will interfere with the ability to undergo therapy including chemotherapy are ineligbile
- •Patients with a history of a different malignancy are ineligible, unless the disease has not progressed for >= 2 years
- •Patient must not have current peripheral neuropathy > grade 2 at time of randomization
- •Patient must not have any co-existing condition that would preclude full compliance with the study; no prior history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
研究组 & 干预措施
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Image Guided Radiation Therapy (Radiation)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm B (docetaxel, cisplatin, carboplatin, surgery, IMRT)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Patients who are ineligible to receive cisplatin receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery no later than 6 weeks following the last dose of chemotherapy. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV or carboplatin IV weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Docetaxel (Drug)
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Image Guided Radiation Therapy (Radiation)
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm A (surgery, IMRT, cisplatin, carboplatin)
Patients undergo standard of care surgery. Beginning 4-6 weeks after surgery, patients undergo image guided IMRT QD for 5 fractions per week for 30 fractions. Patients with positive margins/positive ECS in lymph nodes undergo image guided IMRT QD for 5 fractions per week for 30 fractions and cisplatin IV over 1-2 hours or carboplatin IV over 30 minutes (for patients who are ineligible to receive cisplatin) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: From date of randomization, censoring follow-up at last date of contact, assessed for up to 5 years
Log rank test will be used to compare OS between the two arms. The comparison between the two arms for OS will be conducted separately (each at one-sided 0.05 significance level).
Structure preservation rate defined as both skull base and orbit being preserved
时间窗: Up to 5 years
Fisher's exact test will be used to compare the structure preservation rate between the two arms. The comparison between the two arms for structure preservation will be conducted separately (each at one-sided 0.05 significance level).
次要结局
- Change in accuracy of magnetic resonance imaging (MRI) and fludeoxyglucose F-18 positron emission tomography/computed tomography (FDG PET/CT) to predict orbital and skull base preservation(Baseline and post-chemotherapy)
- OS by imaging biomarkers(From date of randomization, censoring follow-up at last date of contact, assessed at 2 years)