Study Synopsis

148 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.