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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05253651




Registration number
NCT05253651
Ethics application status
Date submitted
14/02/2022
Date registered
24/02/2022
Date last updated
5/11/2024

Titles & IDs
Public title
A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer
Scientific title
An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer
Secondary ID [1] 0 0
2021-002672-40
Secondary ID [2] 0 0
SGNTUC-029
Universal Trial Number (UTN)
Trial acronym
MOUNTAINEER-03
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tucatinib
Treatment: Drugs - trastuzumab
Treatment: Drugs - bevacizumab
Treatment: Drugs - cetuximab
Treatment: Drugs - oxaliplatin
Treatment: Drugs - leucovorin
Treatment: Drugs - levoleucovorin
Treatment: Drugs - fluorouracil

Experimental: Tucatinib Arm - Tucatinib + trastuzumab + mFOLFOX6

Active comparator: Standard of Care Arm - mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab


Treatment: Drugs: tucatinib
300mg given by mouth (orally) twice daily

Treatment: Drugs: trastuzumab
8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.

Treatment: Drugs: bevacizumab
5mg/kg given by IV every 2 weeks

Treatment: Drugs: cetuximab
400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

Treatment: Drugs: oxaliplatin
85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

Treatment: Drugs: leucovorin
400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

Treatment: Drugs: levoleucovorin
200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

Treatment: Drugs: fluorouracil
400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
Up to approximately 6 years
Secondary outcome [2] 0 0
Confirmed objective response rate (cORR) per RECIST v1.1 by BICR
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
PFS per RECIST v1.1 by investigator assessment
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
cORR per RECIST v1.1 by investigator assessment
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [5] 0 0
Duration of response (DOR) per RECIST v1.1 by BICR
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
DOR per RECIST v1.1 by investigator assessment
Timepoint [6] 0 0
Up to approximately 3 years
Secondary outcome [7] 0 0
Time to second progression or death (PFS2)
Timepoint [7] 0 0
Up to approximately 3 years
Secondary outcome [8] 0 0
Incidence of adverse events (AEs)
Timepoint [8] 0 0
Through 30 days after the last study treatment; approximately 1 year
Secondary outcome [9] 0 0
Incidence of dose alterations
Timepoint [9] 0 0
Through 30 days after the last study treatment; approximately 1 year
Secondary outcome [10] 0 0
Trough concentration (Ctrough)
Timepoint [10] 0 0
Approximately 4 months
Secondary outcome [11] 0 0
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score
Timepoint [11] 0 0
Through 30-37 days after the last study treatment; approximately 1 year
Secondary outcome [12] 0 0
Time to meaningful change in EORTC QLQ30 score
Timepoint [12] 0 0
Through 30-37 days after the last study treatment; approximately 1 year

Eligibility
Key inclusion criteria
* Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
* Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory

* If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
* HER2+ disease as determined by a tissue based assay performed at a central laboratory.
* Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
* Radiographically measurable disease per RECIST v1.1 with:

* At least one site of disease that is measurable and that has not been previously irradiated, or
* If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:

* No evidence of brain metastases
* Previously treated brain metastases which are asymptomatic
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior systemic anticancer therapy for colorectal cancer (CRC) in the locally advanced unresectable or metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.

* Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment
* Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
* Previous treatment with anti-HER2 therapy
* Ongoing Grade 3 or higher neuropathy
* Active or untreated gastrointestinal (GI) perforation at the time of screening.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2028
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Townsville Cancer Center - Townsville
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
4814 - Townsville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
South Dakota
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Argentina
State/province [18] 0 0
Other
Country [19] 0 0
Austria
State/province [19] 0 0
Other
Country [20] 0 0
Belgium
State/province [20] 0 0
Other
Country [21] 0 0
Belgium
State/province [21] 0 0
Haine-Saint-Paul
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Brazil
State/province [23] 0 0
Other
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Canada
State/province [26] 0 0
Saskatchewan
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Chile
State/province [27] 0 0
Other
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China
State/province [28] 0 0
Other
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France
State/province [29] 0 0
Other
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France
State/province [30] 0 0
Brest
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Germany
State/province [31] 0 0
Other
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Greece
State/province [32] 0 0
Other
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Hungary
State/province [33] 0 0
Other
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Ireland
State/province [34] 0 0
Other
Country [35] 0 0
Ireland
State/province [35] 0 0
Dublin
Country [36] 0 0
Italy
State/province [36] 0 0
Other
Country [37] 0 0
Italy
State/province [37] 0 0
Avellino
Country [38] 0 0
Italy
State/province [38] 0 0
Firenze
Country [39] 0 0
Japan
State/province [39] 0 0
Other
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Korea, Republic of
State/province [40] 0 0
Other
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Netherlands
State/province [41] 0 0
Other
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Norway
State/province [42] 0 0
Other
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Poland
State/province [43] 0 0
Other
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Portugal
State/province [44] 0 0
Other
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Slovakia
State/province [45] 0 0
Other
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Spain
State/province [46] 0 0
Other
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Switzerland
State/province [47] 0 0
Other
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Taiwan
State/province [48] 0 0
Other
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United Kingdom
State/province [49] 0 0
Other

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 find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also determine what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).

Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:

* mFOLFOX6 alone,
* mFOLFOX6 with bevacizumab, or
* mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.
Trial website
https://clinicaltrials.gov/study/NCT05253651
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
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
Seagen Trial Information Support
Address 0 0
Country 0 0
Phone 0 0
866-333-7436
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05253651