A phase III, randomized, open label study to establish the superiority of metronomic therapy used in addition to the chemotherapy regimen (Paclitaxel and Carboplatin) over the chemotherapy alone for the treatment of advanced unresectable head and neck cancer.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 238
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
Head and neck cancer is one of the commonest malignancy seen in India. Unfortunately 85% of patients are seen in locally advanced stage. Hence majority of the patients fail. Palliative chemotherapy is one of the main treatment options in this situation. However, except in first line situation there is no standard medical treatment, especially when the cost of immunotherapy and targeted medications like cetuximab make this option unfeasible for majority of the patients. Inspite of the cost, the outcomes provided by these medications are at best modest.
The propsosed study is anInvestigator-initiated, Phase III, randomised open label, controlled trial to see whether oral metronomic therapy given along with palliative chemotherapy (Paclitaxel + Carboplatin) to the patient diagnosed with advanced unresectable head and neck cancer increases overall survival compared to patients getting chemotherapy alone (however not the same chemotherapy agents). This is a superiority trial in which PI comparing the physicians choice treatment with oral matronomic chemotherapy erlotinib 150 mg fixed dose celexoxib 200 ng fixed dose oral methotrexate 9 mg/m2 relative chemotherapy of paclitaxel and carboplatin Stratified randomisation site of the tumor and ECOG PS. Patient is going to bear the cost of complication arising from the experimental treatment. This is beneficial to local community as the burden of head and neck cancers is very high in the area with most patients cannot access immunotherapy/ new drugs. If ths regimen demonstrates a survival benefit it will be an alternative that most patients will afford.
This study involves the comparison between oral metronomic therapy (oral drugs of chemotherapy) given with paclitaxel +carboplatin versus chemotherapy alone.
Arms of the study
Arm A: The participants in this arm will receive palliative chemotherapy with paclitaxel carboplatin plus triple OMCT. In each cycle the participants will have 21 days gap.
OMCT will be administered with tablet erlotinib 150 mg (fixed dose) PO OD daily, capsule celecoxib 200 mg (fixed dose) PO BD daily and oral weekly methotrexate 9 mg/m2.
Arm B: Patients on arm B will receive physician choice therapy with one taxane and with one platin which can be Docetaxel (75 mg/m2) on day 1 in 3 weekly cycles, paclitaxel (175 mg/m2) on day 1 in 3 weekly cycles, injection methotrexate (40 mg/m2) weekly (D1, 8 and 15) in 3 weekly cycles, Capecitabine (1250mg/m2 BD, D1-14) 3 weekly or any other suitable choice as per institutional standard.
The outcomes will be compared in terms of survival and also, the toxicities will be monitored.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Advanced head and neck squamous cell cancers planned for palliative chemotherapy, post first line palliative chemotherapy failure
- •Patients who have failed within 6 months of curative treatment, where chemotherapy was a part will be considered.
- •Age : Any age ≥18 years
- •ECOG performance status ≤2
- •Histopathologically or FNAC (Fine needle aspiration cytology) proof of cancer (squamous cell carcinoma).
- •Participants must have normal organ and marrow function as defined below: a) Leukocytes ≥3,000/mcL b) Platelets ≥100,000/mcL c) Total bilirubin < 1.5 × institutional upper limit of normal d) AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal e) Calculated Creatinine clearance > 30 ml/min.
- •The effects of chemotherapy on the developing human fetus are teratogenic.
- •Hence women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- •Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- •Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of protocol.
- •Both men and women of all races and ethnic groups are eligible for this trial.
- •Willing and able to comply with all study requirements.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Participants who are currently receiving any other investigational agents.
- •Patients with QTc prolongation defined as QTc interval greater than 480 ms in view of risk of sudden cardiac death associated with use of ondansetron.
- •Patients in whom an initial evaluation QTc is prolonged but with medical interventions it is restored to normal are eligible for the study.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in study.
- •Uncontrolled intercurrent illness including, but not limited to, active tuberculosis, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, renal failure (on dialysis), active gastrointestinal bleeding, cerebrovascular accidents within last 1 year, inflammatory bowel disease, known hyperkalaemia ( CTCAE version 5 grade 3 or above which is persistent over 1 week) or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients who have uncontrolled hypertension or diabetes or other chronic medical conditions at initial evaluation but in whom these conditions are controlled with medical intervention can be assessed for eligibility.
- •Pregnant women and breastfeeding women are excluded from this study because Chemotherapy agents have the potential for teratogenicity or abortifacient effects.
- •Patients who are able to receive immunotherapy (both financially and medically fit for the same), will be excluded from this study
- •All inclusion and exclusion criteria have to be satisfied for inclusion in the study.
结局指标
主要结局
Overall Survival
时间窗: OS will be defined in months between the date of randomization to date of death. Patients alive at their | last follow ups would be censored
次要结局
- Progression Free Survival(QOL)