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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04499924




Registration number
NCT04499924
Ethics application status
Date submitted
31/07/2020
Date registered
5/08/2020
Date last updated
29/08/2023

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
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
Overall survival (OS) (Phase 3 only)
Timepoint [1] 0 0
60 months
Primary outcome [2] 0 0
Progression-free survival (PFS) per Response evaluation criteria in solid tumors (RECIST) version 1.1 according to investigator assessment (Phase 3 only)
Timepoint [2] 0 0
36 months
Primary outcome [3] 0 0
Incidence of dose-limiting toxicities (DLTs) (Phase 2 only)
Timepoint [3] 0 0
During first cycle of treatment; up to one month
Primary outcome [4] 0 0
Incidence of adverse events (AEs) (Phase 2 only)
Timepoint [4] 0 0
18 months
Primary outcome [5] 0 0
Incidence of laboratory abnormalities (Phase 2 only)
Timepoint [5] 0 0
18 months
Primary outcome [6] 0 0
Incidence of dose modifications (Phase 2 only)
Timepoint [6] 0 0
18 months
Secondary outcome [1] 0 0
Confirmed objective response rate (ORR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
ORR per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Duration of response (DOR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Disease control rate (DCR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
PFS per RECIST v1.1 according to blinded independent central review (BICR) assessment (Phase 3 only)
Timepoint [5] 0 0
36 months
Secondary outcome [6] 0 0
Confirmed ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
Timepoint [6] 0 0
36 months
Secondary outcome [7] 0 0
ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
Timepoint [7] 0 0
36 months
Secondary outcome [8] 0 0
DOR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
Timepoint [8] 0 0
36 months
Secondary outcome [9] 0 0
DCR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
Timepoint [9] 0 0
36 months
Secondary outcome [10] 0 0
Incidence of AEs (Phase 3 only)
Timepoint [10] 0 0
36 months
Secondary outcome [11] 0 0
Incidence of laboratory abnormalities (Phase 3 only)
Timepoint [11] 0 0
36 months
Secondary outcome [12] 0 0
Incidence of dose modifications (Phase 3 only)
Timepoint [12] 0 0
36 months
Secondary outcome [13] 0 0
PFS per RECIST version 1.1 according to investigator assessment (Phase 2 only)
Timepoint [13] 0 0
18 months
Secondary outcome [14] 0 0
Area under the plasma concentration-time curve (AUC) to the time of the last quantifiable concentration (AUClast) of tucatinib (Phase 2 only)
Timepoint [14] 0 0
1 month
Secondary outcome [15] 0 0
AUC to AUClast of paclitaxel (Phase 2 only)
Timepoint [15] 0 0
1 month
Secondary outcome [16] 0 0
Maximum observed concentration (Cmax) of tucatinib (Phase 2 only)
Timepoint [16] 0 0
1 month
Secondary outcome [17] 0 0
Cmax of paclitaxel (Phase 2 only)
Timepoint [17] 0 0
1 month
Secondary outcome [18] 0 0
Time of Cmax (Tmax) of tucatinib (Phase 2 only)
Timepoint [18] 0 0
1 month
Secondary outcome [19] 0 0
Tmax of paclitaxel (Phase 2 only)
Timepoint [19] 0 0
1 month
Secondary outcome [20] 0 0
Trough concentration (Ctrough) of tucatinib (Phase 2 only)
Timepoint [20] 0 0
18 months
Secondary outcome [21] 0 0
Ctrough of paclitaxel (Phase 2 only)
Timepoint [21] 0 0
18 months
Secondary outcome [22] 0 0
Metabolic ratio of tucatinib based on AUC (MRAUC) (Phase 2 only)
Timepoint [22] 0 0
1 month
Secondary outcome [23] 0 0
MRAUC of paclitaxel (Phase 2 only)
Timepoint [23] 0 0
1 month
Secondary outcome [24] 0 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.
Timepoint [24] 0 0
36 months
Secondary outcome [25] 0 0
Change from baseline in health-related quality of life (HRQoL)
Timepoint [25] 0 0
36 months
Secondary outcome [26] 0 0
Utility index values as assessed by the EQ-5D-5L
Timepoint [26] 0 0
36 months

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/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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
31/03/2027
Actual
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
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 website
https://clinicaltrials.gov/ct2/show/NCT04499924
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