Clinical Trial - NCT03043313

Tucatinib (ONT-380) and Trastuzumab in Treating Patients With HER2+ Metastatic Colorectal Cancer


Sponsor: Academic and Community Cancer Research United

Collaborators: National Cancer Institute (NCI)

Information provided by (Responsible party): Sponsor Identifier: NCT03043313

Protocol Info

Short Description: Tucatinib + Trastuzumab in Colorectal Cancer
Long Description: MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined with Trastuzumab in Patients with HER2+ Metastatic Colorectal Cancer
MGH Status: Open
Sponsor: ACCRU
Disease Program: GI

Next Steps

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This phase II trial studies how well the HER2 inhibitor tucatinib (ONT-380, ARRY-380) works in combination with trastuzumab in treating patients with HER2-positive (HER2+) metastatic colorectal cancer (CRC). Tucatinib may stop the growth of tumor cells by blocking HER2, a receptor needed for cell growth in patients with HER2+ tumors. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of HER2+ tumor cells to grow and spread. Giving tucatinib and trastuzumab in combination may work better in treating patients with HER2+ metastatic CRC.
Condition Title Intervention Phase
Colorectal Adenocarcinoma ERBB2 Gene Amplification HER2/Neu Positive KRAS wt Allele NRAS wt Allele Recurrent Colorectal Carcinoma Stage III Colorectal Cancer AJCC v7 Stage IIIA Colorectal Cancer AJCC v7 Stage IIIB Colorectal Cancer AJCC v7 Stage IIIC Colorectal Cancer AJCC v7 Stage IV Colorectal Cancer AJCC v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7 Unresectable Mass Laboratory Biomarker Analysis Trastuzumab Tucatinib Phase 2
Study Type Interventional
Official Title MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer

Primary Outcome Measures

Objective response rate [Time Frame: Up to 4 months] [Designated as safety issue: ]

Secondary Outcome Measures

Clinical best response [Time Frame: Up to 2 years] [Designated as safety issue: ]

Overall survival [Time Frame: From registration to death due to any cause, assessed up to 2 years] [Designated as safety issue: ]

Progression free survival [Time Frame: From registration to the earliest date of documented disease progression, assessed up to 2 years] [Designated as safety issue: ]

Duration of response [Time Frame: Up to 2 years] [Designated as safety issue: ]

Incidence of adverse events of grade 2 and above [Time Frame: Up to 2 years] [Designated as safety issue: ]

Estimated Enrollment: 25
Study Start Date: June 2017
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: June 2020
Arms Assigned Interventions

Experimental:Treatment (tucatinib, trastuzumab)

Patients receive tucatinib PO BID on days 1-21 and trastuzumab IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Given PO


Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Histologically and/or cytologically confirmed and radiographically measurable adenocarcinoma of the colon or rectum that is metastatic and/or unresectable; subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-1 monoclonal antibody (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High, or contraindication to such treatment(s)
  • Molecular testing result from Clinical Laboratory Improvement Act (CLIA)-certified laboratory confirming that the tumor tissue has at least one of the following:
  • HER2 overexpression (3+ immunohistochemistry [IHC]); Note: HER2 2+ IHC is eligible if the tumor is amplified by fluorescence in situ hybridization (FISH)
  • HER2 (ERBB2) amplification by in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH] signal ratio >= 2.0 or gene copy number > 6)
  • HER2 (ERBB2) amplification by CLIA-certified next generation sequencing (NGS) sequencing assay
  • RAS (KRAS and NRAS) wild-type in primary or metastatic tumor tissue
  • At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated; if the patient 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
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 7 days prior to registration)
  • Platelet count >= 75,000/mm^3 (obtained =< 7 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (obtained =< 7 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with known history of Gilbert syndrome and total bilirubin < 3 x ULN and normal aspartate aminotransferase (AST)/alanine aminotransferase (ALT) are eligible, (obtained =< 7 days prior to registration)
  • AST and ALT =< 2.5 x ULN (=< 5 x ULN if liver metastases are present) (obtained =< 7 days prior to registration)
  • Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula (obtained =< 7 days prior to registration)
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless on medication known to alter INR and/or aPTT
  • Left ventricular ejection fraction (LVEF) >= 50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented =< 28 days prior to registration
  • Women of child bearing potential and male partners of women of child bearing potential must agree to use two medically accepted methods of contraception, one of them being a barrier method during the study and for 7 months after the last study drug administration
  • Note: women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopause is defined as amenorrhea >= 12 consecutive months
  • Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
  • Capable of understanding and complying with the protocol requirements and has signed the informed consent document
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to provide mandatory tissue and blood samples for correlative research purposes

Exclusion Criteria:

  • Radiation therapy, hormonal therapy, biologic therapy, experimental therapy, or chemotherapy for cancer =< 21 days prior to registration
  • Prior anti-HER2 targeting therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia and neuropathy; alopecia and neuropathy must have resolved to =< grade 2; congestive heart failure (CHF) must have been =< grade 1 in severity at the time of occurrence and must have resolved completely prior to registration
  • Clinically significant cardiac disease such as history of ventricular arrhythmia requiring therapy, currently uncontrolled hypertension (defined as persistent systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg on antihypertensive medications), or any history of symptomatic CHF
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Patient with known active central nervous system (CNS) metastasis (radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patient is asymptomatic, and no steroids have been administered for at least 30 days)
  • Inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications
  • Use of a strong CYP3A4 inducer or inhibitor, or strong CYP2C8 inducer or inhibitor within 3 elimination half-lives of the inhibitor or inducer prior to first dose of study treatment
  • Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to registration (=< 56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study
  • Serious, non-healing wound, ulcer, or bone fracture
  • History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery =< 6 months prior to registration
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
  • NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • Acute or chronic active hepatitis B or C infection, or other serious chronic infection requiring ongoing treatment
  • Known chronic liver disease, autoimmune hepatitis, or sclerosing cholangitis
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 2 years prior to registration which required systemic treatment
  • EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the local investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

Contacts and Locations

Please refer to this study by its identifier: NCT03043313


  • United States, Arizona
    • Mayo Clinic Hospital Phoenix, Arizona, United States, 85054
    • Mayo Clinic in Arizona Scottsdale, Arizona, United States, 85259
  • United States, Georgia
    • Emory University Hospital/Winship Cancer Institute Atlanta, Georgia, United States, 30322
  • United States, Massachusetts
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, New York
    • Roswell Park Cancer Institute Buffalo, New York, United States, 14263
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • Duke University Medical Center Durham, North Carolina, United States, 27710
  • United States, Wisconsin
    • Aurora Cancer Care-Milwaukee West Wauwatosa, Wisconsin, United States, 53226

Sponsors and Collaborators

Academic and Community Cancer Research United

National Cancer Institute (NCI)

More Information

No publications provided

Responsible Party: Sponsor Identifier: NCT03043313
Other Study ID Numbers: NCI-2017-01107
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Academic and Community Cancer Research United:





Colorectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms

Colonic Neoplasms




Antibodies, Monoclonal


Antineoplastic Agents, Immunological

Next Steps

If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation. processed this data on August 15, 2019