Gastric Cancer Adenocarcinoma MetastaticPhase 2RAINSPOTNCT06962137
Phase II RAINSPOT: Zolbetuximab-Paclitaxel-Ramucirumab for CLDN18.2 Positive Gastro-esophageal Cancer
A Phase 2 study testing zolbetuximab in people with Gastric Cancer Adenocarcinoma Metastatic and Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Universitaire Ziekenhuizen KU Leuven at 6 sites in Belgium.
Trial summary
This study examines whether adding the drug Zolbetuximab to an existing treatment (Paclitaxel and Ramucirumab) can improve patients' survival. The goal is to see if this combination works better for patients whose tumours contain a specific protein (CLDN18.2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Cancer Adenocarcinoma Metastatic, Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- zolbetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 6 sitesBelgium
- Study dates
- 11 Dec 2025to 30 Aug 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age at the time of ICF
- WHO performance status 0 - 1
- Histologically proven metastatic gastroesophageal adenocarcinoma
- Pretreatment with one 1st line therapy according to SOC (+/- immunotherapy)
- If relapse while adjuvant (immune/chemo) therapy or within 6 months ending adjuvant therapy the adjuvant therapy is considered a first line therapy
- CLDN18.2-positive (defined as ≥75% of tumour cells showing moderate-to-strong membranous CLDN18.2 staining, as determined by immunohistochemistry using the VENTANA CLDN18 [43-14A] RxDx Assay.
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- Any PDL1 score
- Use of highly effective methods of birth control
- Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
Who cannot join
- 1. Metastatic squamous cell cancer of the esophagus 2. Absolute contra-indication for anti-VEGF inhibitors (tumor perforation, active proteinuria, recent stroke, myocardial infarction, acute arterial thrombosis, active wound problem) 3. Other active malignancy 4. Pretreatment with Zolbetuximab or other anti-CLDN18.2 direct therapy in first line setting once available.
- 5. Known hypersensitivity to the active substance Zolbetuximab or to any of the excipients [(Arginine, Phosphoric acid (E 338), Sucrose, Polysorbate 80 (E 433)] 6. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive 7. Participation in another interventional Trial with an investigational medicinal product (IMP) or device
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Belgium6 sites, 6 recruiting
- Not yet recruiting
UZA
Antwerp
Timon Vandamme, MD, mocatrials@uza.be
- Not yet recruiting
Cliniques Universitaires Saint-Luc Brussels
Brussels
Marc Van Den Eynde, MD, +32 2 764 11 11, marc.vandeneynde@saintluc.uclouvain.be
- Not yet recruiting
HUB
Brussels
ana-maria.bucalau@hubruxelles.be
- Not yet recruiting
UZ Gent
Ghent
Karen Geboes, MD, +32 9 332 10 73, studies.digonco@uzgent.be
- Recruiting
UZ Leuven
Leuven, 3000
Filip Van Herpe, MD, +32 16 34 42 18, filip.vanherpe@uzleuven.be
Filip Van Herpe, MD
- Not yet recruiting
AZ Delta Roeselare
Roeselare
Pieter Vandecandelaere, MD, +32 (0)51 23 72 15, pieter.vandecandelaere@azdelta.be
About this study
Official title: Phase II RAINSPOT: a Multicentric Open Label Trial of Zolbetuximab-Paclitaxel-Ramucirumab in Second Line Setting for CLDN18.2 Positive Gastro-esophageal Adenocarcinoma
This study examines whether adding the drug Zolbetuximab to an existing treatment (Paclitaxel and Ramucirumab) can improve patients' survival. The goal is to see if this combination works better for patients whose tumours contain a specific protein (CLDN18.2). The results will be compared to past patient data from those who only received the standard treatment.
Zolbetuximab (Vyloy) is a cancer medicine that is used to treat adults with gastric or gastro-esophageal junction adenocarcinoma (a type of cancer of the stomach or the transition between the stomach and esophagus). Zolbetuximab will be administered via an intravenous infusion in combination with Paclitaxel and Ramucirumab (Cyramza) (two other cancer drugs that are the standard treatment for this condition). Treatment will take place at regular intervals in the hospital. In addition to treatment,patients will undergo a tumour biopsy. While the biopsy procedure may cause some discomfort or pain, it will only be performed if medically justifiable. Patients participation in the study will continue as long as they receive treatment and the disease does not worsen. The overall duration of the study, for all patients, will span several years.
- Conditions
- Gastric Cancer Adenocarcinoma Metastatic, Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma
- Being tested
- zolbetuximab, Retrospective cohort, no intervention
- Keywords
- Zolbetuximab-Paclitaxel-Ramucirumab, second line, CLDN18.2 positive, gastro-esophageal adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zolbetuximabDrug
The investigational product, Zolbetuximab, is a sterile lyophilized powder preparation with the chimeric monoclonal antibody Zolbetuximab as the active pharmaceutical ingredient.
Retrospective cohort, no interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Prospective cohort - Zolbetuximab + SOC Palcitaxel and Ramucirumab | Experimental | * Zolbetuximab: 800 mg/m² loading dose of at C1D1, followed by subsequent doses of 400 mg/m² every 2 weeks. Zolbetuximab should be administered after antiemetic premedication but prior to Paclitaxel-Ramucirumab.
* Paclitaxel: 80 mg/m² weekly for 3 weeks followed by a week of break according to routine practice.
* Ramucirumab: 8 mg/kg every 2 weeks according to routine practice. Receives: Drug: zolbetuximab |
| Retrospective cohort | Other | For the retrospective cohort the investigators will identify patients treated with Paclitaxel-Ramucirumab between January 2021 until December 2023 (the era of immunotherapy) in the forementioned centers that have confirmed CLDN18.2 positivity on a baseline biopsy but were not treated with Zolbetuximab in first line setting (nor in experimental setting). Treatment with immunotherapy or targeted therapy in first line setting is allowed. Receives: Other: Retrospective cohort, no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
OS (overall survival)
The primary objective is to evaluate the effect of Zolbetuximab plus Paclitaxel-Ramucirumab on survival in CLDN18.2 positive patients that were previously treated in first line but unexposed to Zolbetuximab or other anti CLDN18.2 targeted therapy.
Measured: From enrollment to the last FU visit of the patient (2 years)
Secondary outcomes (2)
PFS (progression free survival)
PFS, which is defined as the time from the date of signature of informed consent until the date of radiological PD (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or death from any cause, whichever is earliest. Patients unprogressed at time of discontinuation for other causes, starting a subsequent line of treatment will be censored for progression at the start of this subsequent treatment.
Measured: From enrollment till last FU visit of patient (2 years). Data will be reported at the final study report (max 3 years from study start).]
Safety analysis
Safety analysis. Frequency and severity of treatment emergent AEs, SAEs, irAEs. AEs leading to death,discontinuation of trial intervention
Measured: Up to 90 days after last Zolbetuximab dose for each individual patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2025
- Study start11 Dec 2025
- Primary completion31 Dec 2029 (estimated)
- Study completion30 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric Cancer Adenocarcinoma MetastaticStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- The Trial is divided into a prospective open label cohort and a retrospective cohort. There are six participating centers. All patients with known CLDN18.2 positivity at baseline are eligible for the prospective cohort, if they did not receive anti-CLD18.2 therapy as first line therapy. It is acceptable to have the CLDN18.2 information tested during their 1st line therapy. All participants who will be included in the trial will remain on the trial until confirmation of disease progression. For the retrospective cohort the investigators will identify patients treated with Paclitaxel-Ramucirumab between January 2021 until December 2023 (the era of immunotherapy) in the forementioned centers that have confirmed CLDN18.2 positivity on a baseline biopsy but were not treated with Zolbetuximab in first line setting (nor in experimental setting). Treatment with immunotherapy or targeted therapy in first line setting is allowed.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Filip Van Herpe, MD, Principal investigator, Universitaire Ziekenhuizen KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06962137
- Sponsor's protocol ID
- S70358
- Other IDs
- ISR007148, 2025-521358-41-00, 2025
- Acronym
- RAINSPOT
- Status last verified
- Dec 2025
- First submitted
- 24 Apr 2025
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No