Clincosm LogoSign in Get a demo

Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

Sponsor
Seagen Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03043313
Collaborator
National Cancer Institute (NCI) (NIH), Academic and Community Cancer Research United (Other)
117
Enrollment
56
Locations
3
Arms
70.2
Anticipated Duration (Months)
2.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
117 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer
Actual Study Start Date :
Jun 23, 2017
Actual Primary Completion Date :
Mar 28, 2022
Anticipated Study Completion Date :
Apr 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort A: Tucatinib + Trastuzumab

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.

Drug: Trastuzumab
Given intravenously (into the vein; IV)
Other Names:
  • Herceptin

    • Drug: Tucatinib
    Given orally
    Other Names:
  • ARRY-380
  • ONT-380
  • TUKYSA

    		•
    Experimental: Cohort B: Tucatinib + Trastuzumab

    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.

    Drug: Trastuzumab
    Given intravenously (into the vein; IV)
    Other Names:
  • Herceptin

    • Drug: Tucatinib
    Given orally
    Other Names:
  • ARRY-380
  • ONT-380
  • TUKYSA

    		•
    Experimental: Cohort C: Tucatinib Monotherapy

    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.

    Drug: Tucatinib
    Given orally
    Other Names:
  • ARRY-380
  • ONT-380
  • TUKYSA

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Confirmed objective response rate (cORR) per RECIST 1.1 per blinded independent central review (BICR) in pooled Cohorts A+B [Up to 8 months]

      cORR is defined as confirmed complete response (CR) or partial response (PR).

    Secondary Outcome Measures

    1. ORR at 12 weeks of treatment per RECIST 1.1 according to BICR assessment [Up to 12 weeks]

      ORR by Week 12 is defined as the proportion of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.

    2. Duration of response (DOR) per RECIST 1.1 according to BICR assessment [Up to approximately 4 years]

      DOR is defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease or to death due to any cause, whichever comes first.

    3. Progression-free survival (PFS) per RECIST 1.1 according to BICR assessment for pooled Cohorts A+B [Up to approximately 4 years]

      PFS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to first documentation of tumor progression or to death due to any cause.

    4. Overall survival (OS) in pooled Cohorts A+B [Up to approximately 4 years]

      OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.

    5. Incidence of adverse events (AEs) [Through 30 days following last dose; up to approximately 9 months overall per subject]

    6. Incidence of dose modifications [Through 30 days following last dose; up to approximately 9 months overall per subject]

    7. Incidence of laboratory abnormalities [Through 30 days following last dose; up to approximately 9 months overall per subject]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • 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:

    • 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

    Exclusion Criteria

    • 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

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35249
    2 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
    3 Mayo Clinic Arizona Phoenix Arizona United States 85054
    4 Pacific Shores Medical Group Long Beach California United States 90813
    5 Keck Medical Center / University of Southern California Los Angeles California United States 90033
    6 Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute Los Angeles California United States 90048
    7 Stanford University School of Medicine Palo Alto California United States 94304
    8 Saint Joseph Heritage Medical Group Santa Rosa California United States 95403
    9 Rocky Mountain Cancer Centers - Aurora Aurora Colorado United States 80012
    10 Lombardi Cancer Center / Georgetown University Medical Center Washington District of Columbia United States 20007
    11 Florida Cancer Specialists - South Region Fort Myers Florida United States 33901
    12 Florida Cancer Specialists - North Region Saint Petersburg Florida United States 33705
    13 Winship Cancer Institute / Emory University School of Medicine Atlanta Georgia United States 30322
    14 University of Chicago Medical Center Chicago Illinois United States 60637-1470
    15 Indiana University Simon Cancer Center Indianapolis Indiana United States 46202
    16 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    17 University of Kansas Cancer Center Westwood Kansas United States 66205
    18 Massachusetts General Hospital Boston Massachusetts United States 02114
    19 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    20 Karmanos Cancer Institute / Wayne State University Detroit Michigan United States 48201
    21 Mayo Clinic Rochester Rochester Minnesota United States 55905
    22 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    23 Roswell Park Cancer Institute Buffalo New York United States 14203
    24 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    25 Duke University Medical Center Durham North Carolina United States 27710
    26 Case Western Reserve University / University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
    27 Northwest Cancer Specialists, P.C. Portland Oregon United States 97227
    28 Oregon Health and Science University Portland Oregon United States 97239-3098
    29 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    30 Tennessee Oncology-Nashville/Sarah Cannon Research Institute Nashville Tennessee United States 37203
    31 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    32 Texas Oncology - Beaumont Beaumont Texas United States 77702-1449
    33 Texas Oncology - Baylor Sammons Cancer Center Dallas Texas United States 75246
    34 Joe Arrington Cancer Research and Treatment Center Lubbock Texas United States 79410
    35 Texas Oncology - McAllen McAllen Texas United States 78503
    36 Texas Oncology - San Antonio Medical Center San Antonio Texas United States 78240
    37 Texas Oncology - Tyler Tyler Texas United States 75702
    38 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    39 Providence Regional Medical Center Everett Everett Washington United States 98201
    40 Seattle Cancer Care Alliance / University of Washington Seattle Washington United States 98109-1023
    41 Aurora Research Institute Cancer Center Milwaukee Wisconsin United States 53215
    42 Cliniques Universitaires Saint Luc Brussels Other Belgium 1200
    43 Universitair Ziekenhuis Antwerpen Edegem Other Belgium 2650
    44 UZ Leuven campus Gasthuisberg Leuven Other Belgium 3000
    45 Hospitalier Jean Minjoz Besancon Other France 25030
    46 Center Georges Francois Leclerc Dijon Other France 21000
    47 Hôpital Franco-Britannique - Fondation Cognacq-Jay Levallois-Perret Other France 92300
    48 Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes Lyon Other France 69373
    49 Hopital Saint-Antoine Paris Other France 75012
    50 Instituto Europeo di Oncologia Milan Other Italy 20141
    51 Niguarda Ca' Granda Hospital Milan Other Italy 20162
    52 Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara Pisa Other Italy 56126
    53 Hospital Universitario Vall d'Hebron Barcelona Other Spain 08035
    54 Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet) L'Hospitalet de Llobregat Other Spain 08907
    55 Hospital General Universitario Gregorio Maranon Madrid Other Spain 28007
    56 Hospital Clinico Universitario de Valencia Valencia Other Spain 46010

    Sponsors and Collaborators

    • Seagen Inc.
    • National Cancer Institute (NCI)
    • Academic and Community Cancer Research United

    Investigators

    • Study Chair: John H Strickler, Academic and Community Cancer Research United
    • Study Director: Michael Stecher, MD, Seagen Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Seagen Inc.
    ClinicalTrials.gov Identifier:
    NCT03043313
    Other Study ID Numbers:
    • SGNTUC-017
    • NCI-2017-01107
    • ACCRU-GI-1617
    • P30CA015083
    First Posted:
    Feb 6, 2017
    Last Update Posted:
    Jun 8, 2022
    Last Verified:
    Jun 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Seagen Inc.
    HER2
    ERBB2
    Colorectal cancer
    Seattle Genetics
    Additional relevant MeSH terms:
    Colorectal Neoplasms
    Trastuzumab
    Tucatinib

    Study Results

    No Results Posted as of Jun 8, 2022