A Phase II Randomized Trial Evaluating the Use of Proton Pump Inhibitors (PPIs) in Conjunction With Chemotherapy, in Patients With Recurrent Unresectable or Metastatic Cancers of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Time to progression
研究概览
简要总结
The purpose of this study is to determine if the addition of proton pump inhibitors (PPIs) to standard chemotherapy can improve progression free survival in patients with head and neck cancer.
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
- Double (Participant, Investigator)
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
- •Males and non-pregnant, non-lactating females at least 18 years old.
- •Histologically or cytologically confirmed diagnosis of SCCHN (Squamous Cell Carcinoma of the Head and Neck).
- •Stage IVC (metastatic) or advanced, locally recurrent SCCHN not amenable to curative surgery or radiotherapy.
- •Measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumors) vs 1.1 (Appendix 1).
- •a. If the only site of measurable disease for this study is within a prior field of irradiation, then the sum of the longest diameters (SLD) of that lesion must have increased by at least 20% from the prior treatment nadir.
- •ECOG Performance status (measure of health and general well being on a scale of 0 to 5 where 0 represents perfect health) < 1 (Appendix 2).
- •Expected survival of at least 3 months.
- •Adequate liver and renal function that is defined as Calculated creatinine clearance of <30ml/min (by Jelliffe calculator) AST (aspartate aminotransferase)/ALT (alanine aminotransferase) < 2.5 X ULN (unless there are hepatic metastasis, in which case AST/ALT within 5 X ULN) Total Bilirubin < 1.5 X ULN (Appendix 5).
- •Ability to understand and willingness to sign an informed consent form.
- •Willingness and ability to comply with study procedures and follow up.
- •There is no restriction on number of prior therapies as long as the patient is deemed a candidate for palliative chemotherapy with one of the standard chemotherapy regimens.
- •Willingness to use contraception by a method that is deemed effective by the Investigator by both male and female patients of childbearing potential and their partners throughout the treatment period and for at least 30 days following the last cycle of chemotherapy (post menopausal women must have been amenorrheal for at-least 12 months to be considered of non-childbearing potential).
排除标准
- •Comorbidities precluding treatment with combination chemotherapy or per investigator discretion.
- •Pregnancy or lactation.
- •Medical or psychiatric illness that may compromise the patient's ability to tolerate the treatment or comply with the study requirements.
- •Patients with another active cancer or history of another cancer in the last 3 years except those treated with curative intent such as skin cancer (other than melanoma), in situ breast or in situ cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 2 years.
- •Allergy to PPI or inability to tolerate PPI.
- •Patients residing in prison.
- •Any investigational drug dose within 28 days of planned start of trial.
- •Any concurrent standard therapy intended to treat SCCHN.
- •Any symptomatic infection (bacterial, fungal or viral) as per the investigator discretion.
- •Patients with uncontrolled CNS (Central Nervous System) metastases are excluded. Patients with known, previously treated CNS metastases are eligible if they are neurologically stable as per the investigating physician's clinical assessment.
- •Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.
- •Patients on Rilpivirine, Atazanavir, Indinavir and Nelfinavir will not be eligible for participation in study because of the significant drug interaction unless the patient can be switched to a different antiviral medication prior to study enrollment.
- •Omeprazole can increase the serum concentration of methotrexate, clorazepate and citalopram increasing the risk of adverse effects.
- •Omeprazole may result in reduction in clinical efficacy of clopidogrel and increased risk for thrombosis.
- •Omeprazole when co-administered with dasatinib, bosutinib, ponatinib, erlotinib, dabrafenib and vismodegib reduces the systemic exposure to these drugs, therefore patients on these drugs should not be enrolled in the study.
研究组 & 干预措施
Observational
Patients on the Observational arm are currently being treated with a proton pump inhibitor (PPIs) such as Omeprazole. They will receive standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Omeprazole (Drug)
Observational
Patients on the Observational arm are currently being treated with a proton pump inhibitor (PPIs) such as Omeprazole. They will receive standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Carboplatin (Drug)
Observational
Patients on the Observational arm are currently being treated with a proton pump inhibitor (PPIs) such as Omeprazole. They will receive standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: 5FU (Drug)
Observational
Patients on the Observational arm are currently being treated with a proton pump inhibitor (PPIs) such as Omeprazole. They will receive standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Paclitaxel (Drug)
Observational
Patients on the Observational arm are currently being treated with a proton pump inhibitor (PPIs) such as Omeprazole. They will receive standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Pemetrexed (Drug)
Standard Chemo + Placebo
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive placebo along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Carboplatin (Drug)
Standard Chemo + Placebo
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive placebo along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: 5FU (Drug)
Standard Chemo + Placebo
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive placebo along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Paclitaxel (Drug)
Standard Chemo + Placebo
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive placebo along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Pemetrexed (Drug)
Standard Chemo + Omeprazole
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive Omeprazole along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Omeprazole (Drug)
Standard Chemo + Omeprazole
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive Omeprazole along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Carboplatin (Drug)
Standard Chemo + Omeprazole
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive Omeprazole along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: 5FU (Drug)
Standard Chemo + Omeprazole
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive Omeprazole along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Paclitaxel (Drug)
Standard Chemo + Omeprazole
Patients on the Standard Chemo and Placebo arm are not currently being treated with a proton pump inhibitor (PPI). They will be randomized to receive Omeprazole along with standard of care chemotherapy. Standard treatment is the choice of the treating physician and may include Carboplatin in combination with either 5FU, Paclitaxel, or Pemetrexed.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Time to progression
时间窗: 6 months post treatment
The primary aim, progression-free survival, will be defined from start of treatment to date of first progression and will be tested using a Cox proportional hazard regression model with treatment arm as the only predictor.
次要结局
- Median overall survival(6 months post treatment)
- Proportion of patients that experience a response to treatment(6 months post treatment)