NCT03764553

Liposomal iRInotecan, Carboplatin or oXaliplatin for Esophagogastric Cancer

Liposomal iRInotecan, Carboplatin or oXaliplatin in the First Line Treatment of Esophagogastric Cancer: a Randomized Phase 2 Study

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 320 (estimated)
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-center, open label, randomized phase II trial for patients with previously untreated metastatic or locally advanced esophagogastric cancer, using a pick the winner design to identify the best combination therapy in terms of progression free survival and neurotoxicity.

Detailed description

The sample size to identify the best combination therapy is based on the following decision making strategy. With less or even zero neurotoxicity grade 2-4 (defined as worst toxicity), the Nal-IRI plus 5FU/LV combination is expected to outperform the standard combination capecitabine plus oxaliplatin and may also outperform capecitabine plus carboplatin. To compensate for a higher neurotoxicity grade 2-4 level, the capecitabine combinations should demonstrate increased progression free survival (PFS) according to the next schedule. With the addition of nivolumab in the second quarter of 2022, the capecitabine combinations are expected to have a PFS benefit over the Nal-IRI of 0.65 months (50% of the 1.7 months seen in the CM6495, because 50% of the capecitabine regimens will be treated with nivolumab) If the difference in the percentage of patients experiencing neurotoxicity grade 2-4 stays within the 10-30% range, an increase of at least 3.65 months of PFS identifies the most preferable combination strategy; if the percentage is ≤10% and the PFS increase \<3.65 months, but in favor of carboplatin, then the choice should be based on other grade 3-4 toxicities observed; otherwise, the strategy with the lowest level of neurotoxicity grade 2-4 is the most preferable one. At least 4.65 months PFS should be gained to compensate for a difference in neurotoxicity grade 2-4 within the \>30 to 50% range. The total number to be included will be 272. Patients will first be tested for PD-L1 and then will be conditionally randomized. Patients with a PD-L1 CPS \<5 or a contraindication for nivolumab treatment, will be randomized to respectively the Nal-IRI plus 5FU, the capecitabine plus carboplatin and capecitabine plus oxaliplatin group following a 2:1:1 scheme. Patients with a PD-L1 CPS ≥5 will be randomized to the capecitabine plus carboplatin and capecitabine plus oxaliplatin group following a 2:1 scheme and will receive nivolumab in addition to chemotherapy treatment. Taking into account 15% withdrawal of patients from the trial before start of study medication, we will include 320 patients.

Conditions

• Esophageal Cancer

Interventions

Type	Name	Description
DRUG	Liposomal Irinotecan	Iv liposomal irinotecan
DRUG	Carboplatin	IV Carboplatin
DRUG	Capecitabine	PO Capecitabine
DRUG	Oxaliplatin	IV Oxaliplatin
DRUG	5-fluorouracil	IV 5-fluorouracil
DRUG	Leucovorin	IV Leucovorin

Timeline

• Start date: 2019-05-01
• Primary completion: 2025-07-31
• Completion: 2026-07-01
• First posted: 2018-12-05
• Last updated: 2026-04-07

Locations

34 sites across 1 country: Netherlands