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

Official Title

A Randomized, Double-blind, Placebo-controlled, Active Comparator Phase 2/3 Study of Tucatinib in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Subjects With Previously Treated, Locally-advanced Unresectable or Metastatic HER2+ Gastric or Gastroesophageal Junction Adenocarcinoma (GEC)

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.

Trial Description

Primary Outcome:

  • Overall survival (OS) (Phase 3 only)
  • Progression-free survival (PFS) per Response evaluation criteria in solid tumours (RECIST) version 1.1 according to investigator assessment (Phase 3 only)
  • Incidence of dose-limiting toxicities (DLTs) (Phase 2 only)
  • Incidence of adverse events (AEs) (Phase 2 only)
  • Incidence of laboratory abnormalities (Phase 2 only)
  • Incidence of dose modifications (Phase 2 only)
Secondary Outcome:
  • Confirmed objective response rate (ORR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
  • ORR per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
  • Duration of response (DOR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
  • Disease control rate (DCR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
  • PFS per RECIST v1.1 according to blinded independent central review (BICR) assessment (Phase 3 only)
  • Confirmed ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
  • ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
  • DOR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
  • DCR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
  • Incidence of AEs (Phase 3 only)
  • Incidence of laboratory abnormalities (Phase 3 only)
  • Incidence of dose modifications (Phase 3 only)
  • PFS per RECIST version 1.1 according to investigator assessment (Phase 2 only)
  • Area under the plasma concentration-time curve (AUC) to the time of the last quantifiable concentration (AUClast) of tucatinib (Phase 2 only)
  • AUC to AUClast of paclitaxel (Phase 2 only)
  • Maximum observed concentration (Cmax) of tucatinib (Phase 2 only)
  • Cmax of paclitaxel (Phase 2 only)
  • Time of Cmax (Tmax) of tucatinib (Phase 2 only)
  • Tmax of paclitaxel (Phase 2 only)
  • Trough concentration (Ctrough) of tucatinib (Phase 2 only)
  • Ctrough of paclitaxel (Phase 2 only)
  • Metabolic ratio of tucatinib based on AUC (MRAUC) (Phase 2 only)
  • MRAUC of paclitaxel (Phase 2 only)
  • Time to deterioration of GEC symptoms as assessed by the European Organisation for Research and Treatment or Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and EORTC QLQ-OG25 questionnaires.
  • Change from baseline in health-related quality of life (HRQoL)
  • Utility index values as assessed by the EQ-5D-5L

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society