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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04499924




Registration number
NCT04499924
Ethics application status
Date submitted
31/07/2020
Date registered
5/08/2020
Date last updated
25/03/2025

Titles & IDs
Public title
Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer
Scientific 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)
Secondary ID [1] 0 0
C4251004
Secondary ID [2] 0 0
SGNTUC-022
Universal Trial Number (UTN)
Trial acronym
MOUNTAINEER-02
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Adenocarcinoma 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
Esophageal Adenocarcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tucatinib
Treatment: Drugs - trastuzumab
Treatment: Drugs - ramucirumab
Treatment: Drugs - paclitaxel
Other interventions - tucatinib placebo
Other interventions - trastuzumab placebo

Experimental: Phase 2 Arm - Tucatinib + trastuzumab + ramucirumab + paclitaxel

Experimental: Arm 3A - Tucatinib + trastuzumab + ramucirumab + paclitaxel

Active comparator: Arm 3B - Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo

Experimental: Arm 3C - Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo


Treatment: Drugs: tucatinib
300 mg given twice daily orally

Treatment: Drugs: 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

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

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

Other interventions: tucatinib placebo
Given twice daily orally

Other interventions: trastuzumab placebo
IV on Days 1 and 15 of each cycle
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-limiting Toxicities (DLT) During the First Cycle of Treatment
Timepoint [1] 0 0
Cycle 1 (28 days)
Primary outcome [2] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Primary outcome [3] 0 0
Number of Participants With Treatment-emergent Laboratory Abnormalities
Timepoint [3] 0 0
From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Primary outcome [4] 0 0
Number of Participants With Clinically Significant Vital Signs Values
Timepoint [4] 0 0
From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Primary outcome [5] 0 0
Maximum Percentage Change From Baseline in Weight
Timepoint [5] 0 0
From Baseline (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Primary outcome [6] 0 0
Number of Participants With Any Dose Modifications
Timepoint [6] 0 0
From first dose of the study treatment (Day 1) up to the last dose of study treatment (maximum treatment duration up to 19.8 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 By Investigator Assessment
Timepoint [1] 0 0
From the first dose of study treatment until the first documented CR or PR on or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 19.8 months)
Secondary outcome [2] 0 0
Confirmed ORR Per RECIST v1.1 By Investigator Assessment
Timepoint [2] 0 0
From the first dose of study treatment until the first documented confirmed CR or PR or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 19.8 months)
Secondary outcome [3] 0 0
Progression-Free Survival (PFS) Per RECIST v1.1 By Investigator Assessment
Timepoint [3] 0 0
From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (up to 19.8 months)
Secondary outcome [4] 0 0
Duration of Response (DOR) Per RECIST v1.1 By Investigator Assessment
Timepoint [4] 0 0
From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (up to 19.8 months)
Secondary outcome [5] 0 0
Disease Control Rate (DCR) Per RECIST v1.1 By Investigator Assessment
Timepoint [5] 0 0
From the first dose study treatment until PD or death, whichever occurred first (up to 19.8 months)
Secondary outcome [6] 0 0
Area Under the Plasma Concentration-time Curve to the Time of the Last Quantifiable Concentration (AUClast) of Paclitaxel, Tucatinib and Their Metabolites
Timepoint [6] 0 0
Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose; Paclitaxel and its metabolites- Cycle 1 Days 1 and 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Secondary outcome [7] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [7] 0 0
Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Secondary outcome [8] 0 0
Time to Maximum Observed Plasma Concentration (Tmax)
Timepoint [8] 0 0
Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Secondary outcome [9] 0 0
Trough Concentration (Ctrough)
Timepoint [9] 0 0
Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Predose (each cycle length=28 days)
Secondary outcome [10] 0 0
Metabolite Ratio Based on AUClast (MRAUClast)
Timepoint [10] 0 0
Paclitaxel and its metabolites- Cycle 1 Days 1 and 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/04/2024
Sample size
Target
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Central Coast Local Health District (Gosford and Wyong Hospitals) - Gosford
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
63V6 63 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Busan
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Daegu
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seongnam-si
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Suwon-si
Country [28] 0 0
Taiwan
State/province [28] 0 0
Kaohsiung
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
JoAl Mayor, PharmD, BCOP
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04499924