ErbB-2 Inhibitor ARRY-380 and Trastuzumab in Treating Patients With HER2-Positive Metastatic Colon or Rectal Cancer

Description

This phase II trial studies how well ErbB-2 inhibitor ARRY-380 works in combination with trastuzumab in treating patients with HER2-positive colon or rectal cancer that has spread to other places in the body. ErbB-2 inhibitor ARRY-380 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving ErbB-2 inhibitor ARRY-380 and trastuzumab may work better in treating patients with colon or rectal cancer.

Study Start Date

June, 23 2017

Estimated Completion Date

June 2019

Interventions

  • Other: Laboratory Biomarker Analysis
  • Biological: Trastuzumab
  • Drug: ErbB-2 Inhibitor ARRY-380

Study ID

Academic and Community Cancer Research United -- ACCRU-GI-1617

Status

Recruiting

Trial ID

NCT03043313

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

35

Sponsor

Academic and Community Cancer Research United

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, and an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), or have contraindication to such treatment
  • 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 amplification by in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH] signal ratio > 2.0 or gene copy number > 6)
  • HER2 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) obtained =< 7 days prior to registration
  • Aspartate aminotransferase (AST) and alanine aminotransferase (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
  • Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 7 months after the last dose of study drug(s), even if oral contraceptives are also used
  • Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
  • 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 Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible treatment
  • 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 mm Hg and/or diastolic blood pressure > 100 mm Hg 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 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

Gender

All

Ages

18 Years and older

Accepts Healthy Volunteers

No

Study Locations and Contact Information (22)

Study Location Distance Name Phone Email
DanaFarber Cancer Institute - Boston, Massachusetts 2.4 miles Michele Vincitore 617-632-3125 michele_vincitore@dfci.harvard.edu
DanaFarber Cancer Institute - Boston, Massachusetts 2.4 miles Michele Vincitore 617-632-3125 michele_vincitore@dfci.harvard.edu
DanaFarber Cancer Institute - Boston, Massachusetts 2.4 miles Michele Vincitore 617-632-3125 michele_vincitore@dfci.harvard.edu
Memorial SloanKettering Cancer Center - New York, New York 187.1 miles Andrea Cercek None cerceka@mskcc.org
Memorial SloanKettering Cancer Center - New York, New York 187.1 miles Andrea Cercek None cerceka@mskcc.org
Memorial SloanKettering Cancer Center - New York, New York 187.1 miles Andrea Cercek None cerceka@mskcc.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Deeponpaul Singh 716-845-8270 deeponpaul.singh@roswelpark.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Deeponpaul Singh 716-845-8270 deeponpaul.singh@roswelpark.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Deeponpaul Singh 716-845-8270 deeponpaul.singh@roswelpark.org
Duke University Medical Center - Durham, North Carolina 609.0 miles Ireka Burrus 919-668-1861 Ireka.burrus@duke.edu
Duke University Medical Center - Durham, North Carolina 609.0 miles Ireka Burrus 919-668-1861 Ireka.burrus@duke.edu
Duke University Medical Center - Durham, North Carolina 609.0 miles Ireka Burrus 919-668-1861 Ireka.burrus@duke.edu
Aurora Cancer CareMilwaukee West - Wauwatosa, Wisconsin 862.1 miles Jennifer Mathieu 414-302-2312 jennifer.mathieu@aurora.org
Aurora Cancer CareMilwaukee West - Wauwatosa, Wisconsin 862.1 miles Jennifer Mathieu 414-302-2312 jennifer.mathieu@aurora.org
Aurora Cancer CareMilwaukee West - Wauwatosa, Wisconsin 862.1 miles Jennifer Mathieu 414-302-2312 jennifer.mathieu@aurora.org
Emory UniversityWinship Cancer Institute - Atlanta, Georgia 932.0 miles Christina S Wu 404-778-0202 christina.wu@emoryhealthcare.org
Emory UniversityWinship Cancer Institute - Atlanta, Georgia 932.0 miles Christina S Wu 404-778-0202 christina.wu@emoryhealthcare.org
Emory UniversityWinship Cancer Institute - Atlanta, Georgia 932.0 miles Christina S Wu 404-778-0202 christina.wu@emoryhealthcare.org
Mayo Clinic - Rochester, Minnesota 1,083.1 miles Jodi Klocke 507-538-4545 klocke.jodi@mayo.edu
Mayo Clinic in Arizona - Scottsdale, Arizona 2,280.6 miles Laurie A Mihalik 480-342-3256 mihalik.laurie@mayo.edu
Mayo Clinic in Arizona - Scottsdale, Arizona 2,280.6 miles Laurie A Mihalik 480-342-3256 mihalik.laurie@mayo.edu
Mayo Clinic in Arizona - Scottsdale, Arizona 2,280.6 miles Laurie A Mihalik 480-342-3256 mihalik.laurie@mayo.edu

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