Liposomal iRInotecan, Carboplatin or oXaliplatin in the first line treatment of esophagogastric cancer: a randomized phase 2 study (LyRICX)

No globally accepted standard first-line treatment regimen exists.
In deciding on an optimal first-line treatment regimen, not only (progression
free) survival should be taken into account, but also the effects of a
first-line regimen on the possibility to undergo subsequent treatments. In this
respect, side effects are of crucial importance: if a side-effect does not
readily resolve after stopping the treatment this may hamper the start of
second-line treatment. This issue particularly arises with neurotoxicity, a
well-known side effect of the F-oxaliplatin combination. F-oxaliplatin is a
frequently used doublet in many countries, and, in fact, in the Netherlands
even the most frequently used doublet. [publication in preparation]
Neurotoxicity may last for prolonged periods of time, and may prevent the start
of second line paclitaxel. Replacing oxaliplatin by another platinum compound
such as carboplatin, or a non-neurotoxic compound such as liposomal irinotecan,
may resolve this issue.

Therefore, in this study we will set out to compare three F-doublets, both in
terms of efficacy and toxicity, more particularly neurotoxicity, to identify
the most optimal first-line cytotoxic treatment regimen for future use.

As of spring 2022 nivolumab will be added to the treatment of patients with a
PD-L1 CPS of 5 or higher, but this isonly applicable for patients treated with
CapOX or CapCar. For this reason, patients with a CPS of 5 or higher will no
longer be randomized to F-Nal-IRI from that moment on, but only to CapOx and
CapCar and they will also receive nivolumab in addition to chemotherapy.

This study has been transitioned to CTIS with ID 2023-509287-26-00 check the CTIS register for the current data.

To compare the progression free survival and neurotoxity of first line
treatment with F-Nal-IRI, CapCar and CapOx.

multi-center, open label, randomized phase II trial using a pick the winner
design

1. Nal-IRI 70 mg/m² (water free base), folinic acid 400 mg/m², fluorouracil
2400 mg/m² over 46 h, every 2 weeks.
2. Capecitabine 1000 mg/m2 and carboplatin AUC5 with/without Nivolumab, every
three weeks.
3. Capecitabine 1000 mg/m2 and oxaliplatin 130 mg/m2 with/without Nivolumab,
every three weeks.

Burden
Extra VENA PUNCTION: baseline, week 4 and at progression: 55 ml blood
(translational research)
Extra QUESTIONNAIRE: every 3 weeks, neurotoxicity 5-10 min
Extra QUESTIONNAIRE: every 9 weeks 20-30 min
Extra FECES collection and diet diary during 3 days: baseline, week 4, week 10
OPTIONAL: baseline: biopsies primary gastroesophagel tumor and /or
metastases (liver maximal 2-3 extra biopsies, skin 3-4 biopsies)

In regular treatment, a biopsy will performed to diagnose metastatic
cancer. Also every 3 weeks, a physical examination and a venapunction will
take place to assure that the next cycle can be administered.
The blood and tumor tissue for biomarkers, feces collection and questionnaires
are extra.