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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
11/07/2024
Titles & IDs
Public title
Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer
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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)
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Secondary ID [1]
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SGNTUC-022
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Universal Trial Number (UTN)
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Trial acronym
MOUNTAINEER-02
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Gastric Adenocarcinoma
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Gastroesophageal Junction Adenocarcinoma
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Esophageal Adenocarcinoma
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Condition category
Condition code
Cancer
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0
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Oesophageal (gullet)
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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0
Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overall survival (OS) (Phase 3 only)
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Assessment method [1]
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OS is defined as the time from randomization to death due to any cause
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Timepoint [1]
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60 months
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Primary outcome [2]
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Progression-free survival (PFS) per Response evaluation criteria in solid tumors (RECIST) version 1.1 according to investigator assessment (Phase 3 only)
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Assessment method [2]
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PFS is defined as the time from randomization to the date of disease progression or death from any cause
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Timepoint [2]
0
0
36 months
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Primary outcome [3]
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0
Incidence of dose-limiting toxicities (DLTs) (Phase 2 only)
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Assessment method [3]
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0
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Timepoint [3]
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0
During first cycle of treatment; up to one month
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Primary outcome [4]
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Incidence of adverse events (AEs) (Phase 2 only)
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Assessment method [4]
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0
An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
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Timepoint [4]
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0
18 months
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Primary outcome [5]
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Incidence of laboratory abnormalities (Phase 2 only)
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Assessment method [5]
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0
To be summarized using descriptive statistics.
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Timepoint [5]
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18 months
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Primary outcome [6]
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0
Incidence of dose modifications (Phase 2 only)
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Assessment method [6]
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0
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Timepoint [6]
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0
18 months
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Secondary outcome [1]
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0
Confirmed objective response rate (ORR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
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Assessment method [1]
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0
ORR is defined as the proportion of subjects with best overall response of CR or PR
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Timepoint [1]
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36 months
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Secondary outcome [2]
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0
ORR per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
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Assessment method [2]
0
0
ORR is defined as the proportion of subjects with best overall response of CR or PR
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Timepoint [2]
0
0
36 months
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Secondary outcome [3]
0
0
Duration of response (DOR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
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Assessment method [3]
0
0
DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause
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Timepoint [3]
0
0
36 months
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Secondary outcome [4]
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0
Disease control rate (DCR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
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Assessment method [4]
0
0
DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)
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Timepoint [4]
0
0
36 months
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Secondary outcome [5]
0
0
PFS per RECIST v1.1 according to blinded independent central review (BICR) assessment (Phase 3 only)
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Assessment method [5]
0
0
PFS is defined as the time from randomization to the date of disease progression or death from any cause
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Timepoint [5]
0
0
36 months
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Secondary outcome [6]
0
0
Confirmed ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
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Assessment method [6]
0
0
ORR is defined as the proportion of subjects with best overall response of CR or PR
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Timepoint [6]
0
0
36 months
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Secondary outcome [7]
0
0
ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
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Assessment method [7]
0
0
ORR is defined as the proportion of subjects with best overall response of CR or PR
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Timepoint [7]
0
0
36 months
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Secondary outcome [8]
0
0
DOR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
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Assessment method [8]
0
0
DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause
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Timepoint [8]
0
0
36 months
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Secondary outcome [9]
0
0
DCR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
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Assessment method [9]
0
0
DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)
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Timepoint [9]
0
0
36 months
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Secondary outcome [10]
0
0
Incidence of AEs (Phase 3 only)
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Assessment method [10]
0
0
An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
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Timepoint [10]
0
0
36 months
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Secondary outcome [11]
0
0
Incidence of laboratory abnormalities (Phase 3 only)
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Assessment method [11]
0
0
To be summarized using descriptive statistics.
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Timepoint [11]
0
0
36 months
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Secondary outcome [12]
0
0
Incidence of dose modifications (Phase 3 only)
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Assessment method [12]
0
0
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Timepoint [12]
0
0
36 months
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Secondary outcome [13]
0
0
PFS per RECIST version 1.1 according to investigator assessment (Phase 2 only)
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Assessment method [13]
0
0
PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause
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Timepoint [13]
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18 months
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Secondary outcome [14]
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0
Area under the plasma concentration-time curve (AUC) to the time of the last quantifiable concentration (AUClast) of tucatinib (Phase 2 only)
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Assessment method [14]
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Pharmacokinetic (PK) parameter
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Timepoint [14]
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1 month
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Secondary outcome [15]
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AUC to AUClast of paclitaxel (Phase 2 only)
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Assessment method [15]
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PK parameter
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Timepoint [15]
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0
1 month
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Secondary outcome [16]
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Maximum observed concentration (Cmax) of tucatinib (Phase 2 only)
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Assessment method [16]
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PK parameter
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Timepoint [16]
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1 month
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Secondary outcome [17]
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Cmax of paclitaxel (Phase 2 only)
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Assessment method [17]
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PK parameter
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Timepoint [17]
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0
1 month
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Secondary outcome [18]
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0
Time of Cmax (Tmax) of tucatinib (Phase 2 only)
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Assessment method [18]
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PK parameter
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Timepoint [18]
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1 month
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Secondary outcome [19]
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0
Tmax of paclitaxel (Phase 2 only)
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Assessment method [19]
0
0
PK parameter
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Timepoint [19]
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0
1 month
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Secondary outcome [20]
0
0
Trough concentration (Ctrough) of tucatinib (Phase 2 only)
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Assessment method [20]
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0
PK parameter
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Timepoint [20]
0
0
18 months
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Secondary outcome [21]
0
0
Ctrough of paclitaxel (Phase 2 only)
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Assessment method [21]
0
0
PK parameter
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Timepoint [21]
0
0
18 months
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Secondary outcome [22]
0
0
Metabolic ratio of tucatinib based on AUC (MRAUC) (Phase 2 only)
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Assessment method [22]
0
0
PK parameter
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Timepoint [22]
0
0
1 month
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Secondary outcome [23]
0
0
MRAUC of paclitaxel (Phase 2 only)
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Assessment method [23]
0
0
PK parameter
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Timepoint [23]
0
0
1 month
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Secondary outcome [24]
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0
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.
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Assessment method [24]
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The EORTC questionnaires measure aspects of health-related quality of life (HRQoL). Time to deterioration will be assessed in specific pre-specified single items from either the EORTC QLQ-C30 or EORTC QLQ OG25 and deterioration is defined as a 10-point increase from baseline in the symptom scales and a 10-point decrease from baseline for overall HRQoL.
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Timepoint [24]
0
0
36 months
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Secondary outcome [25]
0
0
Change from baseline in health-related quality of life (HRQoL)
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Assessment method [25]
0
0
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Timepoint [25]
0
0
36 months
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Secondary outcome [26]
0
0
Utility index values as assessed by the EQ-5D-5L
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Assessment method [26]
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The EQ-5D-5L questionnaire is used as a preference based measurement of HRQoL outcomes. Data will be summarized using descriptive statistics.
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Timepoint [26]
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36 months
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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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
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
22/03/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
17/04/2024
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Sample size
Target
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Accrual to date
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Final
17
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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0
Central Coast Local Health District (Gosford and Wyong Hospitals) - Gosford
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Recruitment hospital [2]
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0
Austin Health - Heidelberg
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Recruitment postcode(s) [1]
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0
2250 - Gosford
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Recruitment postcode(s) [2]
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63V6 63 - Heidelberg
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Alabama
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Country [2]
0
0
United States of America
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State/province [2]
0
0
Arizona
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Country [3]
0
0
United States of America
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State/province [3]
0
0
California
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Colorado
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Country [5]
0
0
United States of America
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State/province [5]
0
0
District of Columbia
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Country [6]
0
0
United States of America
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State/province [6]
0
0
Illinois
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Country [7]
0
0
United States of America
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State/province [7]
0
0
Iowa
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Country [8]
0
0
United States of America
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State/province [8]
0
0
Kentucky
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Country [9]
0
0
United States of America
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State/province [9]
0
0
Massachusetts
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Country [10]
0
0
United States of America
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State/province [10]
0
0
Minnesota
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Country [11]
0
0
United States of America
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State/province [11]
0
0
Nevada
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Country [12]
0
0
United States of America
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State/province [12]
0
0
New York
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Country [13]
0
0
United States of America
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State/province [13]
0
0
North Carolina
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Country [14]
0
0
United States of America
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State/province [14]
0
0
Ohio
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Country [15]
0
0
United States of America
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State/province [15]
0
0
Oregon
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Country [16]
0
0
United States of America
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State/province [16]
0
0
Pennsylvania
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Country [17]
0
0
United States of America
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State/province [17]
0
0
Tennessee
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Country [18]
0
0
United States of America
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State/province [18]
0
0
Texas
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Country [19]
0
0
United States of America
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State/province [19]
0
0
Utah
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Country [20]
0
0
United States of America
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State/province [20]
0
0
Washington
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Country [21]
0
0
Canada
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State/province [21]
0
0
Ontario
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Country [22]
0
0
Canada
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State/province [22]
0
0
Quebec
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Country [23]
0
0
Korea, Republic of
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State/province [23]
0
0
Busan
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Country [24]
0
0
Korea, Republic of
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State/province [24]
0
0
Daegu
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Country [25]
0
0
Korea, Republic of
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State/province [25]
0
0
Seongnam-si
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Country [26]
0
0
Korea, Republic of
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State/province [26]
0
0
Seoul
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Country [27]
0
0
Korea, Republic of
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State/province [27]
0
0
Suwon-si
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Country [28]
0
0
Taiwan
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State/province [28]
0
0
Kaohsiung
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Country [29]
0
0
Taiwan
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State/province [29]
0
0
Taipei
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Country [30]
0
0
United Kingdom
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State/province [30]
0
0
London
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Country [31]
0
0
United Kingdom
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State/province [31]
0
0
Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Seagen Inc.
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT04499924
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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0
JoAl Mayor, PharmD, BCOP
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Address
0
0
Seagen Inc.
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04499924
Download to PDF