A randomized, open-label, parallel group, phase III randomized trial to evaluate the efficacy and tolerability of Olanzapine in patients receiving Multi-day highly emetogenic chemotherapy (HEC) with Aprepitant based antiemetic prophylaxis. (OM-HEC study)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- ICMR
- 入组人数
- 148
- 试验地点
- 1
研究概览
简要总结
Study Synopsis148 adult cancer patients will be randomized into two arms:Arm A – NK1 RA + 5-HT3 RA + Dexamethasone + Olanzapine Arm B – NK1 RA + 5-HT3 RA + Dexamethasone Primary endpoint is Complete Response (CR) (no vomiting + no rescue meds); secondary endpoints include acute/delayed CR, toxicity, and quality of life (FLIE).
Background:
CINV significantly affects treatment tolerance and quality of life. Olanzapine is effective for single-day HEC, but its benefit in multi-day HEC is unproven, creating the need for this study.
Rationale:Multi-day chemotherapy causes overlapping acute and delayed emesis. The trial investigates whether adding olanzapine provides superior nausea/vomiting control compared to standard therapy alone.Hypothesis: Olanzapine-containing regimen yields higher CR rates than non-olanzapine regimen.Primary Objective: Primary objective is to compare overall (0–120 hr) CR rates. Secondary objectives include acute and delayed CR, tolerability, and quality of life assessment.Inclusion Criteria:Adults more than equal to 18 years with a diagnosed malignancy who are planned for multi-day high emetogenic chemotherapy (e.g., BEP, Ifosfamide-based, cisplatin + etoposide, DCF, transplant conditioning). They must have ECOG 0–2, adequate organ function, no vomiting within 24 hours, and be willing to consent and comply with study procedures.Exclusion Criteria:Patients are excluded if they have significant CNS disease, cognitive impairment, or have recently used antipsychotics or antiemetics. Those with uncontrolled infections/diabetes/cardiac disease, alcohol abuse, hypersensitivity to olanzapine, or inability to swallow oral medications are also excluded.
Study Design:Single-centre, randomized, parallel-group, open-label phase III study conducted at Tata Memorial Hospital.Study Assessments: Includes baseline evaluation, patient diary completion, daily nausea/vomiting monitoring, telephonic follow-up (D2–D5), mid-cycle assessment (D7–10), and end-of-cycle review with AE documentation.Efficacy measurements:Efficacy measured by CR, vomiting episodes, nausea VAS scores, and rescue medication use. Safety assessed using CTCAE v5.0 with documentation of AEs, SAEs, SARs, and SUSARs.Quality of Life:Assessed using the FLIE questionnaire at baseline, mid-cycle, and prior to Cycle 2.Data management and Statistics:Block randomization (1:1), sample size 148. Analyses performed using nonparametric tests and log-rank methods.Ethics and Conduct: Study approved by IEC and conducted per ICH-GCP and NDCT 2019. Includes data retention, compensation rules, and dissemination plans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Diagnosis of malignant disease.
- •Patients scheduled to receive multi day high emetic risk chemotherapy regimen.
- •Majority and not all of them are enlisted below Cisplatin plus Etoposide with or without additional drugs such as Bleomycin or Ifosfamide VeIP regimen include Vinblastine, Ifosfamide, Cisplatin High-dose Ifosfamide Ifosfamide with Doxorubicin Ifosfamide with Etoposide based regimens Dacarbazine based regimens for lymphoma or sarcoma BEAM or FEAM or high dose Melphalan dose greater than or equal to 140 milligrams per square meter or high dose Cyclophosphamide Total body irradiation plus multidrug chemotherapy for stem cell transplant conditioning Carboplatin plus Etoposide Busulfan plus Cyclophosphamide for transplant Doxorubicin plus Cisplatin Docetaxel plus Cisplatin plus 5 Fluorouracil
- •Age greater than or equal to 18 years.
- •ECOG performance status should be 0 to
- •Subjects must have normal organ and marrow function
- •No nausea or vomiting more than 24 hours prior to participation.
- •Negative pregnancy test done less than or equal to 7 days prior to participation, for women of childbearing potential only and as per clinician discretion.
- •Women of reproductive potential who agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial.
- •Patient willing and able to comply with all study requirements including treatment and able to be followed up at regular intervals and or nature of required assessments
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •1.Patients with severe cognitive compromise.
- •2.Patients with a history of CNS disease brain metastases seizure disorder etc
- •Treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone more than or equal to 30 days before participation or planned during protocol therapy
- •The patient has taken or received any medication with known or potential antiemetic activity within the 24 hour period prior to receiving study drugs.
- •This is inclusive of, but not limited to 5 HT3 antagonists, metoclopramide, benzodiazepines, phenothiazines, haloperidol, oral or intravenous steroids, antihistamines, domperidone, olanzapine, antipsychotics.
- •Concurrent abdominal radiotherapy.
- •Chronic alcoholism as determined by the investigator
- •Known hypersensitivity to olanzapine.
- •Medical conditions such as uncontrolled infection including HIV, uncontrolled diabetes mellitus, or cardiac disease, which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
- •Patients who cannot swallow oral formulations of the agents.
- •Patients unwilling to participate in the study.
研究者
Dr Prabhat Bhargava
Tata Memorial Centre , Mumbai