A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Rate of pathologic complete response
研究概览
简要总结
This is a non-randomized open-label investigator initiated pilot study comparing follow-up therapy of advanced head and neck cancer subjects initially treated with triple induction chemotherapy. Subjects will receive surgical treatment or combined chemoradiation therapy based on the subject's apparent clinical response. Spared use of radiation therapy for selective patients who have a complete response to induction chemotherapy could improve well being of this patient population without compromising survival.
详细描述
An important observation of the induction triple chemotherapy regimen know as TPF is that there was an unprecedented high proportion of patients treated who had a complete response of their disease upon the completion of the induction phase. In a recent study by Haddad, et al., a biopsy was performed in all patients following induction chemotherapy and before starting concomitant chemoradiotherapy. Patients with an incomplete response to chemoradiotherapy or who had N3 disease had a neck dissection 6 to 12 weeks after chemoradiotherapy. Twenty-nine neck dissections were performed after chemoradiotherapy. The neck dissection result was pathologically positive in 7 (24%) patients (all alive with no evidence of disease) and negative in 22 (76%) patients (21 alive with no evidence of disease). Post-TPF, primary site biopsy result was negative in 64 patients (89%) and positive in 8 patients (11%). While the protocol required all patients to subsequently receive concomitant chemoradiation regardless of disease response to the induction component of the regimen, it is reasonable to question whether the complete responder subset really needed to undergo the same intensive chemoradiation treatment compared to the partial responders. Thus, a less intense therapy may be sufficient. The long term goal of this protocol is to alter the model of highly effective cancer therapy from what is maximally tolerated by the patient to what is minimally necessary for a cure.
One treatment strategy for patients with advanced head and neck cancer who prove to be highly sensitive to chemotherapy is to combine the modalities of polychemotherapy and conservation surgery with the goal of avoiding radiation therapy. For those patients whose primary disease is classified as T2-3 (resectable), and who have a complete response following induction therapy, it is feasible to perform an organ preservation tumor nidusectomy at the primary site to verify that the clinical complete response is truly pathological complete response. Similarly, the clinical complete response observed for the associated nodal disease, can be verified pathologically by performing a selective neck dissection without causing significant morbidity. Both tumor nidusectomy and selective neck dissection has been shown to be an effective adjuvant in this setting. Building on these observations, the novel protocol outlined in this proposal has the potential to spare the use of radiation therapy for selective patients who have a complete response to induction chemotherapy and thereby improve their well being without compromising survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 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
- •Ability to understand and the willingness to sign a written informed consent document.
- •Histologically confirmed Stage III-IV (T1, T2, T3) (N0-N2) squamous cell carcinoma of the oropharynx staged according to AJCC guidelines.
- •The subject must be considered surgically resectable via a transoral approach at the time of presentation.
- •Age >18 years
- •Life expectancy >/= 5 years
- •ECOG performance status <2
- •Subject must have measurable disease, at least one lesion accurately measured in at least one dimension as >10 mm with CT scan.
- •Hematologic Absolute neutrophil count > 1,000/mm3, Hemoglobin > 8.0 g/dl Platelet count > 100,000/mm3 Leukocytes >3,000/mcL
- •Hepatic Total Bilirubin ≤ ULN; AST and ALT and Alkaline Phosphatase within the eligible range
- •Renal - creatinine within normal institutional limits or >60 mL/min/1.73 m2 creatinine > institutional normal
- •Women of childbearing potential with negative pregnancy test.
- •Men and women of childbearing age willing to use effective contraception
排除标准
- •N3 nodal disease according to AJCC guidelines
- •Retropharyngeal nodal involvement
- •Second primary head and neck tumor unless it is/was a basal or squamous cell skin cancer
- •Prior surgery, chemotherapy, biologic or radiotherapy for a head or neck malignancy
- •Concurrent investigational agent or intervention (within 90 days of screening visit)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxol, cisplatin, 5- fluorouracil, or carboplatin.
- •History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
- •Breastfeeding women
- •Pre-existing peripheral neuropathy grade > 3
- •Evidence of distant metastatic disease
- •Unknown primary site
- •Prior or concurrent malignancies (excluding adequately treated basal or squamous cell skin cancer, in situ cervical cancer, stage I or II cancer from which the subject has been in complete remission for at least 12 months (excluding head and neck), any cancer from which the subject has been cancer free for 5 years)
- •History of allergies to any of the pre-medications.
- •Investigator consideration based upon screening interview and/or procedures
- •Evidence of bone invasion/destruction
- •Uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women
- •History of HIV, hepatitis B, hepatitis C, or delta antigen
- •Known allergy to India Ink or methylene blue
结局指标
主要结局
Rate of pathologic complete response
时间窗: 42 months
To assess the rate of pathologic complete response of subjects (based on analysis of the surgical specimen), in both the primary site as well as the lymph nodes, with resectable stage III-IV squamous cell carcinoma of the oropharynx treated with TPF induction chemotherapy followed by conservation (organ preservation) surgery for clinically complete responders
次要结局
- 2 year overall survival(42 months)
- Clinical complete response(42 months)
- 2 year disease-free survival(42 months)
- Quality of life(42 months)
- Incidence of HPV and EGFR positivity(42 months)
- K-ras mutational analysis(42 months)