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

NCT ID: NCT04499924

Last Updated: 2025-01-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-22

Study Completion Date

2024-04-17

Brief Summary

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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.

Detailed Description

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Conditions

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Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Esophageal Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Phase 2 Arm

Tucatinib + trastuzumab + ramucirumab + paclitaxel

Group Type EXPERIMENTAL

tucatinib

Intervention Type DRUG

300 mg given twice daily orally

trastuzumab

Intervention Type DRUG

6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter

ramucirumab

Intervention Type DRUG

8 mg/kg will be administered IV on Days 1 and 15 of each cycle

paclitaxel

Intervention Type DRUG

60 or 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle

Arm 3A

Tucatinib + trastuzumab + ramucirumab + paclitaxel

Group Type EXPERIMENTAL

tucatinib

Intervention Type DRUG

300 mg given twice daily orally

trastuzumab

Intervention Type DRUG

6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter

ramucirumab

Intervention Type DRUG

8 mg/kg will be administered IV on Days 1 and 15 of each cycle

paclitaxel

Intervention Type DRUG

60 or 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle

Arm 3B

Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo

Group Type ACTIVE_COMPARATOR

ramucirumab

Intervention Type DRUG

8 mg/kg will be administered IV on Days 1 and 15 of each cycle

paclitaxel

Intervention Type DRUG

60 or 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle

tucatinib placebo

Intervention Type OTHER

Given twice daily orally

trastuzumab placebo

Intervention Type OTHER

IV on Days 1 and 15 of each cycle

Arm 3C

Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo

Group Type EXPERIMENTAL

tucatinib

Intervention Type DRUG

300 mg given twice daily orally

ramucirumab

Intervention Type DRUG

8 mg/kg will be administered IV on Days 1 and 15 of each cycle

paclitaxel

Intervention Type DRUG

60 or 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle

trastuzumab placebo

Intervention Type OTHER

IV on Days 1 and 15 of each cycle

Interventions

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tucatinib

300 mg given twice daily orally

Intervention Type DRUG

trastuzumab

6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter

Intervention Type DRUG

ramucirumab

8 mg/kg will be administered IV on Days 1 and 15 of each cycle

Intervention Type DRUG

paclitaxel

60 or 80 mg/m\^2 IV on Days 1, 8, and 15 of each cycle

Intervention Type DRUG

tucatinib placebo

Given twice daily orally

Intervention Type OTHER

trastuzumab placebo

IV on Days 1 and 15 of each cycle

Intervention Type OTHER

Other Intervention Names

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TUKYSA, ONT-380, ARRY-380 CYRAMZA

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seagen Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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JoAl Mayor, PharmD, BCOP

Role: STUDY_DIRECTOR

Seagen Inc.

Michelle Ubowski, PharmD

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

Arizona Cancer Center / University of Arizona

Tucson, Arizona, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

UCLA Medical Center / David Geffen School of Medicine

Santa Monica, California, United States

Site Status

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, United States

Site Status

Cancer Centers of Colorado - Denver

Denver, Colorado, United States

Site Status

SCL Health - St. Mary's Hospital & Medical Center

Grand Junction, Colorado, United States

Site Status

SCL Health Good Samaritan Medical Center Cancer Centers of Colorado

Lafayette, Colorado, United States

Site Status

Lutheran Medical Center - Cancer Centers of Colorado

Wheat Ridge, Colorado, United States

Site Status

Lombardi Cancer Center / Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Holden Comprehensive Cancer Center / University of Iowa

Iowa City, Iowa, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Minnesota Oncology Hematology P.A.

Saint Paul, Minnesota, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, United States

Site Status

Oncology Associates of Oregon

Eugene, Oregon, United States

Site Status

University of Pennsylvania / Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Tennessee

Knoxville, Tennessee, United States

Site Status

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States

Site Status

Central Coast Local Health District (Gosford and Wyong Hospitals)

Gosford, , Australia

Site Status

Austin Health

Heidelberg, , Australia

Site Status

London Regional Cancer Program, London Health Sciences Centre

London, Ontario, Canada

Site Status

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Site Status

McGill University Department of Oncology / McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center - Oncology

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Ajou University Hospital

Suwon, , South Korea

Site Status

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Sarah Cannon Research Institute UK

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Canada South Korea Taiwan United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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C4251004

Identifier Type: OTHER

Identifier Source: secondary_id

SGNTUC-022

Identifier Type: -

Identifier Source: org_study_id

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