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Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03043313
Recruitment Status : Recruiting
First Posted : February 6, 2017
Last Update Posted : January 18, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Information provided by (Responsible Party):
Seattle Genetics, Inc.

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-postive (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
Metastatic Colorectal Adenocarcinoma Drug: Trastuzumab Drug: Tucatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 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 : June 23, 2017
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

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 Name: Herceptin

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

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 Name: Herceptin

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

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




Primary Outcome Measures :
  1. Confirmed objective response rate (cORR) per RECIST 1.1 per blinded independent central review (BICR) in pooled Cohorts A+B [ Time Frame: 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 [ Time Frame: Up to 12 weeks ]
  2. Duration of response (DOR) per RECIST 1.1 according to BICR assessment [ Time Frame: Up to approximately 4 years ]
  3. Progression-free survival (PFS) per RECIST 1.1 according to BICR assessment for pooled Cohorts A+B [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject ]
  6. Incidence of dose modifications [ Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject ]
  7. Incidence of laboratory abnormalities [ Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 recent 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 laboratory, meeting at least one of the following criteria:

    • HER2+ overexpression (3+ immunohistochemistry [IHC])by an FDA-approved HER2 ICH test
    • HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH]))
    • HER2 (ERBB2) amplification by CLIA-certified 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

    o 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 CYP2C8 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.

    o Exceptions are malignancies with a negligible risk of metastasis or death

  • Subjects with known active CNS metastasis o 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03043313


Contacts
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Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
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United States, Arizona
Mayo Clinic Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Theresa Araque    480-301-2048    Bekaii-saab.tanios@mayo.edu   
Principal Investigator: Tanios Bekaii-Saab         
United States, Georgia
Winship Cancer Institute / Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Trafina Jadhav    404-778-1900    Trafina.jadhav@emory.edu   
Principal Investigator: Christina Wu         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Larissa Masnyk    617-632-3000    Larissa_Masnyk@dfci.harvard.edu   
Principal Investigator: Kimmie Ng         
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Lucas Hamann    507-284-0923    Hamann.Lucas@mayo.edu   
Principal Investigator: Joleen Hubbard, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14203
Contact: Karen Hicks    716-845-8556    Karen.Hicks@RoswellPark.org   
Principal Investigator: Christos Fountzilas         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Asha Krishnan    646-227-3010    krishna2@mskcc.org   
Principal Investigator: Andrea Cercek         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Ireka Burrus    919-668-1861    ireka.burrus@duke.edu   
Principal Investigator: John Strickler         
United States, Wisconsin
Aurora Research Institute Cancer Center Recruiting
Milwaukee, Wisconsin, United States, 53215
Contact: Karen Globke    414-302-2304    Karen.Globke@aurora.org   
Principal Investigator: Federico Sanchez         
Sponsors and Collaborators
Seattle Genetics, Inc.
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Investigators
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Study Chair: John H Strickler Academic and Community Cancer Research United
Study Director: Michael Stecher, MD Seattle Genetics, Inc.

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Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT03043313    
Other Study ID Numbers: SGNTUC-017
NCI-2017-01107 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCRU-GI-1617 ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 6, 2017    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 15, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seattle Genetics, Inc.:
HER2
ERBB2
Colorectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents