Nilatinib Maleate Tablets Combined With Capecitabine in the Treatment of HER2-positive Advanced Esophageal/Esophagogastric Junction/Gastric Adenocarcinoma With Brain Metastases

NCT06374888 | Not Yet Recruiting Phase 2

• 1 other identifier: CVL009-2002
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the efficacy of nilatinib maleate tablets combined with capecitabine in the treatment of HER2-positive advanced esophageal/esophagogastric junction/gastric adenocarcinoma with brain metastasis.

Conditions

Her2-positive Advanced Esophageal/Esophagogastric Junction/Gastric Adenocarcinoma With Brain Metastasis

Keywords

Her2-positive; esophageal; esophagogastric junction; gastric adenocarcinoma; brain metastasis

Outcome Measures

Primary Outcomes (1)

• Objective response rates of the central nervous system as assessed by the Independent Imaging Evaluation Committee based on RECIST1.1

  Objective response rates: Proportion of patients whose tumor volume shrinks by 30% and is maintained for more than 4 weeks

  Throughout the study for approximately 3.5 years

Secondary Outcomes (6)

• Central nervous response rate

  Throughout the study for approximately 3.5 years

• Objective response rates outside the central nervous system

  Throughout the study for approximately 3.5 years

• Disease control rate

  Throughout the study for approximately 3.5 years

• Duration of reaction

  Throughout the study for approximately 3.5 years

• Clinical benefit rate

  Throughout the study for approximately 3.5 years

Study Arms (1)

Single-arm

EXPERIMENTAL

Cohort A: : Patients with brain metastases who had not previously received central nervous system radiotherapy, distance from the last systemic treatment junction The beam should be longer than 2 weeks. Cohort B: Patients with disease progression or new lesions after whole brain radiotherapy or stereotactic radiotherapy; For accepted offices For partially treated lesions, there is clear evidence of progress in imaging examination, and the lesions that have received radiotherapy can be selected as target diseases

Drug: Neratinib maleate in combination with capecitabine

Interventions

Neratinib maleate in combination with capecitabine DRUG

Neratinib maleate tablets，Tablets, 40mg/ tablet, 180 tablets/bottle, orally, 240mg once daily, sealed, stored not above 25℃

Single-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old
• Histologically or cytologically confirmed advanced esophageal/esophagogastric junction/gastric adenocarcinoma with brain metastases (clear imaging evidence of metastasis)
• Tumor tissue was HER2 positive Her2-positive is defined as immunohistochemical (IHC) 3+ or IHC 2+ and in situhybridization (ISH) positive
• Presence of a measurable lesion according to RECIST 1.1: presence of at least one non-radiation-treated lesion with a diameter ≥10 mm (lymph node lesion with a diameter ≥15 mm) that can be accurately measured at baseline on CT or MRI and can be repeatedly measured. If study participants only have lesions after radiotherapy, and the lesions have been clearly identified as radiological progression and can be measured, they can be selected as target lesions. The brain lesion must have a measurable target lesion, but it is not required to have a measurable targetlesion outside the brain
• Corticosteroid dose did not increase one week before brain MRI examination
• There is no limit to previous treatment options, including chemotherapy, radiotherapy, targeted drugs, antibody coupling drugs, immunosuppressants, etc
• Cohort A: Patients with brain metastases who have not previously received central nervous system radiotherapy should be more than 2 weeks from the end of the last systemic therapy. Patients who developed new brain lesions after craniotomy were allowed to be included if they had not received postoperative radiotherapy and were at least 2 weeks removed from surgery.
• Cohort B: Patients with disease progression or new lesions after whole brain radiotherapy or stereotactic radiotherapy; For lesions that have received local treatment, there is clear evidence of progress in imaging examination, and those that have received radiotherapy can be selected as target lesions. Patients with multiple central nervous system lesions, only one or a few of which received stereotactic radiotherapy, and those with lesions that did not receive local treatment, may still participate in the study
• Predicted survival ≥8 weeks
• Women of reproductive age should agree to use contraceptives (such as Iuds, contraceptives or condoms) during the study period and for 6 months after the study ends; Have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be a non-lactating patient; Men should consent to patients who must use contraception during the study period and for 6 months after the end of the study period
• The patient can understand the situation of this study, and the patient and (or) legal representative voluntarily agree to participate in this trial and sign the informed consent

You may not qualify if:

• Participants who have received chemotherapy or radiation therapy (including study drugs) within 2 weeks prior to study participation, or who have not fully recovered from adverse events (excluding hair loss) due to taking drugs for more than 4 weeks
• Patients who have previously received anti-HER2 small-molecule TKI therapy progression
• More than two seizures in the first 4 weeks of enrollment
• Participants currently receiving any other study drug
• History of allergic reactions caused by compounds chemically or biologically similar to neratinib
• Concurrent use of enzyme-induced antiepileptic drugs (EIED), including phenytoin, carbamazepine, oxamazepine, phophenytoin, phenobarbital, pentobarbital, or primidone
• Patients who were receiving any concurrent treatment for cancer during the study period, such as concurrent chemotherapy, radiation, or hormone therapy. Concurrent treatment with bisphosphonates is permitted, but should be started before the first dose of nelatinib
• Present with co-existing medical conditions, including but not limited to persistent or active infections, symptomatic congestive heart failure, unstable angina, arrhythmia, or mental illness/social conditions that would limit compliance with study requirements
• Patients with known contraindications to MRI, such as pacemakers, shrapnel, or ocular foreign bodies
• Patients with pial metastasis only
• Severe malabsorption syndrome or inability to tolerate oral drugs
• Any chronic disease that causes diarrhea with CTCAE≥2 at baseline
• Women who are breastfeeding or whose blood or urine pregnancy test results are positive within 7 days before the first dosing of the study treatment
• The investigators identified patients with any conditions that compromised patient safety, interfered with study evaluation, or had poor adherence

Sponsors & Collaborators

• Convalife (Shanghai) Co., Ltd.: lead

MeSH Terms

Conditions

Brain Neoplasms

Interventions

neratinib; Capecitabine

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

xiaobing chen, ph.D

CONTACT

13937100233; zlyychenxb0807@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Her2-positive advanced esophageal/esophagogastric junction/gastric adenocarcinoma with brain metastases

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 19, 2024
• Study Start: April 30, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): July 30, 2027
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share