An Exploratory Pilot Study of Nab-paclitaxel Based Induction Chemotherapy Followed by Response-Stratified Locoregional Therapy for Patients With Stage III and IV HPV-Related Oropharyngeal Cancer - the OPTIMA HPV Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1
研究概览
简要总结
This phase II trial studies nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and carboplatin followed by response-based local therapy in treating patients with stage III or IV human papillomavirus (HPV)-related oropharyngeal cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, hydroxyurea, fluorouracil, paclitaxel, and cisplatin, 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 spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving nab-paclitaxel and carboplatin before chemoradiation may make the tumor smaller and reduce the amount of chemotherapy and radiation therapy needed. Assigning chemotherapy and radiation therapy based on response (response-based therapy) and giving patients who are responding well lower doses of treatment may help reduce the occurrence of side effects.
详细描述
PRIMARY OBJECTIVES:
I. To determine the 2-year progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. Clinical complete response rate (nab-paclitaxel based induction, compared to European Prospective Investigation into Cancer and Nutrition [EPIC] induction [paclitaxel based]).
II. Response rate (nab-paclitaxel based induction, compared to EPIC induction [paclitaxel based]).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 have pathologically confirmed HPV-positive squamous cell carcinoma
- •HPV testing must follow the following criteria
- •HPV testing using an E6/E7 based assay is preferred, and does not require any validation (e.g. HPV in situ hybridization [ISH] or HPV E6/E7 polymerase chain reaction [PCR])
- •For oropharyngeal tumors p16 immunohistochemistry (IHC) positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan/Lingen et al 2012); it is recommended that p16 IHC positivity is validated at a later point (during or after treatment) using an E6/E7 based test at the University of Chicago and provided slides will be used
- •For non-operative (OP) tumors accurate HPV testing (i.e. ISH, or E6/E7 based testing) is required for enrollment and treatment initiation
- •Availability of >= 10 unstained 5 micron slides
- •Patients with American Joint Committee on Cancer (AJCC) (7th edition, 2010) nodal stage N2 or N3 or a T4 primary tumor
- •The primary and nodal involvement must be assessable on clinical exam (mucosal and lymph node exam)
- •The primary and nodal involvement must have been defined bi- or uni-dimensional measurements measurable by RECIST
- •No previous radiation or chemotherapy for a head and neck cancer
- •No surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy of the tumor is acceptable)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky >= 70%)
- •Leukocytes >= 3000/mm^3
- •Platelets >= 100,000/mm^3
- •Absolute neutrophil count >= 1,500
- •Hemoglobin > 9.0 gm/dL
- •Albumin > 2.9 gm/dL
- •Total bilirubin =< 1.5 mg/dl
- •Creatinine clearance > 45 mL/min (or serum creatinine [SCr] =< 1.5 mg/dL), normal within 2 weeks prior to start of treatment
- •The standard Cockcroft and Gault formula or the measured glomerular filtration rate must be used to calculate creatinine clearance (CrCl) for enrollment or dosing
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper limit of normal (ULN)
- •Alkaline phosphatase =< 2.5 X ULN
- •Patients must sign a study-specific informed consent form prior to study entry; patients should have the ability to understand and the willingness to sign a written informed consent document
排除标准
- •Unequivocal demonstration of distant metastases (M1 disease)
- •Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival; including but not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance
- •Pregnant and nursing women are excluded; men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy; women with child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (B-hCG) pregnancy test at screening
- •Other coexisting malignancies or malignancies diagnosed within the previous 3 years no evidence of disease for at least 3 years; exceptions to this include non-melanoma skin cancer, cervical cancer in situ, well differentiated thyroid cancer or prostate cancer; other cancers that per assessment of the PI are not prognosis limiting can be allowed after review by the PI
- •Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor; residual tumor is required for enrollment on study
- •Patients receiving other investigational agents
- •Peripheral neuropathy >= grade 1
研究组 & 干预措施
Group A (radiation therapy alone)
Patients undergo radiation therapy once daily for weeks.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Group A (radiation therapy alone)
Patients undergo radiation therapy once daily for weeks.
干预措施: carboplatin (Drug)
Group A (radiation therapy alone)
Patients undergo radiation therapy once daily for weeks.
干预措施: radiation therapy (Radiation)
Group A (radiation therapy alone)
Patients undergo radiation therapy once daily for weeks.
干预措施: laboratory biomarker analysis (Other)
Group A (radiation therapy alone)
Patients undergo radiation therapy once daily for weeks.
干预措施: quality-of-life assessment (Procedure)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: radiation therapy (Radiation)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel (Drug)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: hydroxyurea (Drug)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Group B (combination chemotherapy, low-dose radiation therapy)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive low-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Procedure)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: carboplatin (Drug)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: radiation therapy (Radiation)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: paclitaxel (Drug)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: fluorouracil (Drug)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: hydroxyurea (Drug)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: cisplatin (Drug)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: laboratory biomarker analysis (Other)
Group C (combination chemotherapy, high-dose radiation)
Patients receive hydroxyurea PO BID on days 0-5, fluorouracil IV continuously on days 1-5, and paclitaxel IV over 60 minutes on day 1. Patients also receive standard-dose radiation therapy BID on days 1-5. Treatment repeats every 14 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.*
*NOTE: At the discretion of the PI, patients may receive cisplatin IV over 1-3 hours every 3 weeks during radiation therapy instead of paclitaxel and undergo daily radiation therapy.
干预措施: quality-of-life assessment (Procedure)
结局指标
主要结局
Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1
时间窗: Time from enrollment until disease progression or death from any cause, assessed at 2 years
If all patients are followed for two years, the PFS rate and confidence interval will be determined based on the exact binomial distribution. Otherwise, PFS will be estimated using the Kaplan-Meier method and a (large-sample) one-sided 90% confidence interval will be derived for the PFS rate at two years to test the non-inferiority hypothesis. Median PFS will be estimated as described in Brookmeyer and Crowley.
次要结局
- Rate of Pathologic Complete Response (PCR) on Post Treatment Biopsy/Surgery, Evaluated Using RECIST v1.1(Up to 8 weeks after completion of CRT)
- Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only(Up to 5 years)
- Overall Survival(From the date of registration to the date of death or date of last patient contact if censored, assessed up to 5 years)
- Cancer-specific Survival(Up to 5 years)
- Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement(Up to 5 years)
- Rates of Late Toxicity, Determined by Incidence of Xerostomia, Dental Decay, Osteroradionecrosis, G-tube Dependency, Tracheostomy Placement and Dysphagia(Up to 5 years)