Metastatic Colorectal AdenocarcinomaPhase 2NCT03043313
Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
A Phase 2 study testing Trastuzumab and Tucatinib in people with Metastatic Colorectal Adenocarcinoma, run by Seagen Inc. at 56 sites in 5 countries.
Trial summary
This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Adenocarcinoma
- What is being tested?
- Trastuzumab and Tucatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 56 sitesin 5 countries
- Study dates
- 23 Jun 2017to 2 Nov 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
- Unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High.
- Have progression of unresectable or metastatic CRC after the last systemic therapy, or be intolerant of last systemic therapy
- Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS testing
- Willing and able to provide the most recently available tissue blocks obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor
- Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a Clinical Laboratory Improvement Act (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory, meeting at least one of the following criteria:
Show all 13Show fewer
- HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved or Conformité Européene (CE)-marked HER2 ICH test
- HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH]))
- HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited next generation sequencing (NGS) sequencing assay
- Have radiographically measurable disease assessable by RECIST 1.1, 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 (PS) of 0, 1, or 2
- Life expectancy greater than 3 months
- Have adequate hematological, hepatic, renal, coagulation, and cardiac function
Who cannot join
- Previous treatment with anti-HER2 targeting therapy
- Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment
- Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
- Alopecia and neuropathy, which must have resolved to ≤ Grade 2
- Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely
- Anemia, which must have resolved to ≤ Grade 2
Show all 22Show fewer
- Decreased ANC, which must have resolved to ≤ Grade 2
- Have clinically significant cardiopulmonary disease
- Have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment
- Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or anticipation of need for major surgical procedure during the study
- Serious, non-healing wound, ulcer, or bone fracture
- Known to be positive for hepatitis B by surface antigen expression
- Known to have active hepatitis C infection
- Exception for participants with a documented sustained virologic response of 12 weeks
- Known to be positive for human immunodeficiency virus (HIV)
- Subjects who are pregnant, breastfeeding, or planning a pregnancy
- Inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications
- Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a strong CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment
- History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
- Exceptions are malignancies with a negligible risk of metastasis or death
- Subjects with known active CNS metastasis
- Irradiated or resected lesions are permitted, provided the lesions are fully treated and inactive, subject is asymptomatic, and no steroids have been administered for at least 30 days
Trial locations and contacts
56 sites in 5 countries.
56 sites in 5 countries
United States41 sites
Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia, 30322
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado, 80012
Texas Oncology - Beaumont
Beaumont, Texas, 77702-1449
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14203
University of Chicago Medical Center
Chicago, Illinois, 60637-1470
Case Western Reserve University / University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Texas Oncology - Baylor Sammons Cancer Center
Dallas, Texas, 75246
Karmanos Cancer Institute / Wayne State University
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Providence Regional Medical Center Everett
Everett, Washington, 98201
Florida Cancer Specialists - South Region
Fort Myers, Florida, 33901
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Pacific Shores Medical Group
Long Beach, California, 90813
Keck Medical Center / University of Southern California
Los Angeles, California, 90033
Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, 79410
Texas Oncology - McAllen
McAllen, Texas, 78503
Aurora Research Institute Cancer Center
Milwaukee, Wisconsin, 53215
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stanford University School of Medicine
Palo Alto, California, 94304
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Northwest Cancer Specialists, P.C.
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239-3098
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Texas Oncology - San Antonio Medical Center
San Antonio, Texas, 78240
Saint Joseph Heritage Medical Group
Santa Rosa, California, 95403
Seattle Cancer Care Alliance / University of Washington
Seattle, Washington, 98109-1023
Florida Cancer Specialists - North Region
St. Petersburg, Florida, 33705
Texas Oncology - Tyler
Tyler, Texas, 75702
Lombardi Cancer Center / Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
University of Kansas Cancer Center
Westwood, Kansas, 66205
France5 sites
Hospitalier Jean Minjoz
Besançon, Other, 25030
Center Georges Francois Leclerc
Dijon, Other, 21000
Hôpital Franco-Britannique - Fondation Cognacq-Jay
Levallois-Perret, Other, 92300
Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
Lyon, Other, 69373
Hopital Saint-Antoine
Paris, Other, 75012
Spain4 sites
Hospital Universitario Vall d'Hebron
Barcelona, Other, 08035
Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
L'Hospitalet de Llobregat, Other, 08907
Hospital General Universitario Gregorio Maranon
Madrid, Other, 28007
Hospital Clinico Universitario de Valencia
Valencia, Other, 46010
Belgium3 sites
Cliniques Universitaires Saint Luc
Brussels, Other, 1200
Universitair Ziekenhuis Antwerpen
Edegem, Other, 2650
UZ Leuven campus Gasthuisberg
Leuven, Other, 3000
Italy3 sites
Instituto Europeo di Oncologia
Milan, Other, 20141
Niguarda Ca' Granda Hospital
Milan, Other, 20162
Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara
Pisa, Other, 56126
About this study
Official title: MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer
This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body.
In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.
- Conditions
- Metastatic Colorectal Adenocarcinoma
- Being tested
- Trastuzumab, Tucatinib
- Keywords
- HER2, ERBB2, Colorectal cancer, Seattle Genetics
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
Given intravenously (into the vein; IV)
TucatinibDrug
Also called ARRY-380, ONT-380, TUKYSA
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Tucatinib + Trastuzumab | Experimental | Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. Receives: Drug: Trastuzumab; Drug: Tucatinib |
| Cohort B: Tucatinib + Trastuzumab | Experimental | Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. Receives: Drug: Trastuzumab; Drug: Tucatinib |
| Cohort C: Tucatinib Monotherapy | Experimental | Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab. Receives: Drug: Tucatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters.
Measured: Up to 46.6 months
Secondary outcomes (13)
ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment
ORR per BICR by 12 Weeks was defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever came earlier. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than <1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameter.
Measured: Up to 3 months
Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment
DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than <1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (PBSD) (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD. PD was defined as: at least one new malignant lesion, which also includes any lymph node that was normal at baseline (<1.0 cm short axis) and increased to more than or equal to (>=)1.0 cm short axis during follow-up or at least a 20% increase in PBSD taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.
Measured: Up to 64.1 months
Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B
PFS was defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as: at least one new malignant lesion, which also included any lymph node that was normal at baseline (<1.0 cm short axis) and increased to >=1.0 cm short axis during follow-up or at least a 20% increase in post-baseline sum of the diameters (PBSD) taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.
Measured: Up to 64.1 months
Overall Survival (OS) in Pooled Cohorts A+B
OS was defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.
Measured: Up to 71.8 months
Number of Participants With Adverse Events (AEs): Interim Analysis
AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab). Serious AE (SAE): An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE.
Measured: Up to 49.3 months
Number of Participants With AEs: Final Analysis
AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab). SAE: An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to NCI CTCAE version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE.
Measured: Up to 65.1 months
Number of Participants With AEs Resulting in Dose Modification: Interim Analysis
Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.
Measured: Up to 49.3 months
Number of Participants With AEs Resulting in Dose Modification: Final Analysis
Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued. Drug interruption included infusion interrupted (full dose received within 24hrs).
Measured: Up to 65.1 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis
The following hematology laboratory parameters were assessed: Hemoglobin decreased; leukocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Measured: Up to 49.3 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis
The following hematology laboratory parameters were assessed: Hemoglobin decreased; hemoglobin increased; leukocytes decreased; lymphocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Measured: Up to 65.1 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis
The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 was used for creatinine increased. NCI CTCAE v4.03 was used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Measured: Up to 49.3 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis
The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased; albumin decreased; calcium corrected for albumin decreased; calcium corrected for albumin increased; glomerular filtration rate (GFR), estimated decreased; glucose decreased; glucose increased; sodium decreased; sodium increased; calcium and ionized increased. Treatment emergent laboratory abnormalities: Abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 used for creatinine increased. NCI CTCAE v4.03 used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Measured: Up to 65.1 months
Number of Participants With Clinically Significant Vital Signs: Final Analysis
Vital signs included temperature, oxygen saturation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and weight. Vital signs were considered clinically significant: temperature: >= 38 degree Celsius (C); oxygen saturation less than (<)88%; SBP >=120 millimeters of mercury (mmHg) or DBP >=80 mmHg; SBP >=140 mmHg or DBP >=90 mmHg; SBP >=160 mmHg or DBP >=100 mmHg and heart rate >100 beats per minute (bpm) and maximum decrease from baseline in weight in kilograms (kg).
Measured: Up to 65.1 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2017 (estimated)
- Study start23 Jun 2017
- Primary completion28 Mar 2022
- Study completion2 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seagen Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI), Academic and Community Cancer Research United
- Responsible party
- Sponsor
- Investigators
- John H Strickler, Study chair, Academic and Community Cancer Research UnitedJorge Ramos, DO, Study director, Seagen Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03043313
- Sponsor's protocol ID
- SGNTUC-017
- Other IDs
- NCI-2017-01107, ACCRU-GI-1617, P30CA015083
- Status last verified
- Oct 2024
- First submitted
- 31 Jan 2017
- Last updated
- 26 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5.
PubMed 39368039Strickler JH, Bekaii-Saab TS. A study to learn how well tucatinib plus trastuzumab works for treating participants with metastatic colorectal cancer, and how safe it is: a plain language summary of the MOUNTAINEER study. Future Oncol. 2024 Mar;20(8):409-421. doi: 10.2217/fon-2023-0676. Epub 2023 Nov 8.
PubMed 37941353Casak SJ, Horiba MN, Yuan M, Cheng J, Lemery SJ, Shen YL, Fu W, Moore JN, Li Y, Bi Y, Auth D, Fesenko N, Kluetz PG, Pazdur R, Fashoyin-Aje LA. FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer. Clin Cancer Res. 2023 Nov 1;29(21):4326-4330. doi: 10.1158/1078-0432.CCR-23-1041.
PubMed 37318379Strickler JH, Cercek A, Siena S, Andre T, Ng K, Van Cutsem E, Wu C, Paulson AS, Hubbard JM, Coveler AL, Fountzilas C, Kardosh A, Kasi PM, Lenz HJ, Ciombor KK, Elez E, Bajor DL, Cremolini C, Sanchez F, Stecher M, Feng W, Bekaii-Saab TS; MOUNTAINEER investigators. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023 May;24(5):496-508. doi: 10.1016/S1470-2045(23)00150-X.
PubMed 37142372
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03043313
- Acronym / sponsor ID
- SGNTUC-017
- Conditions
- Metastatic Colorectal Adenocarcinoma
- Keywords
- HER2, ERBB2, Colorectal cancer, Seattle Genetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Seagen Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI), Academic and Community Cancer Research United
- Study start
- 23 Jun 2017 (actual)
- Primary completion
- 28 Mar 2022 (actual)
- Study completion
- 2 Nov 2023 (actual)
- First posted
- 6 Feb 2017 (estimated)
- Results
- Posted 18 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body.
In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Tucatinib + Trastuzumab | Experimental | Drug: Trastuzumab, Drug: TucatinibNon-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. |
| Cohort B: Tucatinib + Trastuzumab | Experimental | Drug: Trastuzumab, Drug: TucatinibRandomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. |
| Cohort C: Tucatinib Monotherapy | Experimental | Drug: TucatinibRandomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
- Unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High.
- Have progression of unresectable or metastatic CRC after the last systemic therapy, or be intolerant of last systemic therapy
- Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS testing
- Willing and able to provide the most recently available tissue blocks obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor
Key exclusion criteria (22 listed)
- Previous treatment with anti-HER2 targeting therapy
- Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment
- Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
- Have clinically significant cardiopulmonary disease
- Have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: HerceptinGiven intravenously (into the vein; IV) | Drug | Cohort A: Tucatinib + Trastuzumab, Cohort B: Tucatinib + Trastuzumab |
| TucatinibAlso: ARRY-380, ONT-380, TUKYSAGiven orally | Drug | Cohort A: Tucatinib + Trastuzumab, Cohort B: Tucatinib + Trastuzumab, Cohort C: Tucatinib Monotherapy |
Primary outcome
Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
Time frame: Up to 46.6 months
cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters.
13 secondary outcomes
ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment
Time frame: Up to 3 months
Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment
Time frame: Up to 64.1 months
Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B
Time frame: Up to 64.1 months
Overall Survival (OS) in Pooled Cohorts A+B
Time frame: Up to 71.8 months
Number of Participants With Adverse Events (AEs): Interim Analysis
Time frame: Up to 49.3 months
Number of Participants With AEs: Final Analysis
Time frame: Up to 65.1 months
Number of Participants With AEs Resulting in Dose Modification: Interim Analysis
Time frame: Up to 49.3 months
Number of Participants With AEs Resulting in Dose Modification: Final Analysis
Time frame: Up to 65.1 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis
Time frame: Up to 49.3 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis
Time frame: Up to 65.1 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis
Time frame: Up to 49.3 months
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis
Time frame: Up to 65.1 months
Number of Participants With Clinically Significant Vital Signs: Final Analysis
Time frame: Up to 65.1 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39368039Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5.
- Derived from this study: PubMed 37941353Strickler JH, Bekaii-Saab TS. A study to learn how well tucatinib plus trastuzumab works for treating participants with metastatic colorectal cancer, and how safe it is: a plain language summary of the MOUNTAINEER study. Future Oncol. 2024 Mar;20(8):409-421. doi: 10.2217/fon-2023-0676. Epub 2023 Nov 8.
- Derived from this study: PubMed 37318379Casak SJ, Horiba MN, Yuan M, Cheng J, Lemery SJ, Shen YL, Fu W, Moore JN, Li Y, Bi Y, Auth D, Fesenko N, Kluetz PG, Pazdur R, Fashoyin-Aje LA. FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer. Clin Cancer Res. 2023 Nov 1;29(21):4326-4330. doi: 10.1158/1078-0432.CCR-23-1041.
- Derived from this study: PubMed 37142372Strickler JH, Cercek A, Siena S, Andre T, Ng K, Van Cutsem E, Wu C, Paulson AS, Hubbard JM, Coveler AL, Fountzilas C, Kardosh A, Kasi PM, Lenz HJ, Ciombor KK, Elez E, Bajor DL, Cremolini C, Sanchez F, Stecher M, Feng W, Bekaii-Saab TS; MOUNTAINEER investigators. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023 May;24(5):496-508. doi: 10.1016/S1470-2045(23)00150-X.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John H Strickler study chair
Academic and Community Cancer Research United
Jorge Ramos, DO study director
Seagen Inc.
56 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab and Tucatinib in people with Metastatic Colorectal Adenocarcinoma, run by Seagen Inc. at 56 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, France, Spain, Belgium, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B (time frame: Up to 46.6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03043313, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.