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Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer

About

Brief Summary

This study is being done to see if tucatinib with trastuzumab, ramucirumab and paclitaxel works better than ramucirumab and paclitaxel to treat HER2-positive (HER2+) cancer of the gut (stomach or gastroesophageal cancer). This study will also look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer.

Study treatment will be given in 28-day cycles. In the Phase 2 part of the trial, participants and their doctors will know what drugs are being given (open-label). In the Phase 3 part, the study is "blinded." This means that participants, their doctor, and the study sponsor will not know which drugs are being given.

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase II/III

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC)
  • HER2+ disease documented since progression of the most recent line of systemic therapy, as follows:
    • Phase 2 paclitaxel dose optimization stage:
      • HER2 amplification in a blood-based NGS assay performed at a central laboratory, or
      • HER2 overexpression/amplification immunohistochemistry (IHC) and in situ hybridization (ISH) (IHC3+ or IHC2+/ISH+) assay of a tumor tissue sample
    • Phase 2 dose expansion stage:
      • Cohort 2A: HER2 amplification in a blood-based NGS assay performed at a central laboratory
      • Cohort 2B: No HER2 amplification by blood-based NGS assay, but HER2 overexpression/amplification by IHC and ISH (IHC3+ or IHC2+/ISH+) assay of a tumor tissue sample
    • Phase 3: HER2 amplification in a blood-based NGS assay performed at a central laboratory
  • History of prior treatment with a HER2-directed antibody
  • Progressive disease during or after first-line therapy for locally-advanced unresectable or metastatic GEC
  • Phase 2: Measurable disease according to RECIST version 1.1
  • Phase 3: Measurable or non-measurable disease according to RECIST version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Life expectancy of at least 3 months, in the opinion of the investigator

Exclusion Criteria:

  • Subjects with squamous cell or undifferentiated GEC
  • Having received more than 1 line of prior systemic therapy for locally-advanced unresectable or metastatic disease
  • Having received taxanes ≤12 months prior to enrollment, prior treatment with ramucirumab, or prior treatment with tucatinib, lapatinib, neratinib, afatinib, or any other investigational anti-HER2 and/or anti-EGFR tyrosine kinase inhibitor, or with T-DM1, T-Dxd, or any other HER2-directed antibody-drug conjugate
  • Phase 2 paclitaxel dose optimization stage only: history of prior partial or total gastrectomy
  • Unable to swallow pills

Join this Trial

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Study Stats
Protocol No.
20-001682
Category
Hematology-Oncology
Oncology
Contact
Lisa Yonemoto
Location
  • UCLA Santa Monica
  • UCLA Westwood
For Providers
NCT No.
NCT04499924
For detailed technical eligibility, visit ClinicalTrials.gov.