Skip to main content
Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

The purpose of this study is to assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab on progression-free survival (PFS) per RECIST 1.1 based on independent central review.

Official Title

Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma (HER2CLIMB)

Details

A randomized, international, multi-center, double-blinded study in patients with pretreated unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane, trastuzumab, pertuzumab and T-DM1. Patients will be randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab.

Stratification factors include presence or history of treated or untreated brain metastases (yes/no), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs. 1), and region of world (US vs Canada vs Rest of World).

No crossover from placebo to tucatinib will be allowed.

Safety assessments will be performed at a minimum of once every three weeks throughout study treatment and 30 days after the last dose of study drugs. Laboratory assessments will be performed locally at sites. Cardiac ejection fraction will be assessed by MUGA/ECHO at screening and once every 12 weeks thereafter.

Brain MRI will be performed at baseline in all patients. Efficacy assessments utilize RECIST 1.1 and should include measurement of all known sites of metastatic or locally advanced unresectable disease at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain will be required on this same schedule only in those patients with brain metastases. All treatment decisions will be made based upon investigator assessment of radiologic scans. All patients will undergo a repeat MRI of the brain within 30 days of the end of treatment. Patients in both arms of the study will continue to be followed for OS after completion of study treatment.

Keywords

HER2 Positive Breast Cancer Tucatinib Capecitabine Trastuzumab Xeloda Herceptin Breast Cancer ARRY-380 ONT-380 HER2 Positive Breast Carcinoma HER2 Positive Locally Advanced Breast Cancer HER-2 Positive Breast Cancer HER-2 Positive Breast Carcinoma HER-2 Positive Locally Advanced Breast Cancer Recurrent Breast Carcinoma Stage IV Breast Cancer Metastatic Breast Cancer Breast Carcinoma Metastatic Malignant Neoplasm in the Brain Brain Metastases in Breast Cancer Asymptomatic Brain Metastases in Breast Cancer Low Symptomatic Brain Metastases in Breast Cancer

Eligibility

You can join if…

Open to people ages 18 years and up

Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by fluorescence in situ hybridization (FISH) and/or 3+ staining by immunohistochemistry (IHC)

Have received previous treatment with a taxane, trastuzumab, pertuzumab, and T-DM1

Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy

Have measurable or non-measurable disease assessable by RECIST 1.1

Be at least 18 years of age at time of consent

Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

Have adequate hepatic and renal function

Have left ventricular ejection fraction (LVEF) ≥ 50%

CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:

No evidence of brain metastases

Untreated brain metastases not needing immediate local therapy

Previously treated brain metastases

  1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy
  2. Patients treated with CNS local therapy for newly identified lesions found on initial MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met:

    i. Time since whole brain radiation therapy (WBRT) is> 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is> 7 days prior to first dose of study treatment, or time since surgical resection is> 28 days

    ii. Other sites of evaluable disease are present

    c. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

You CAN'T join if...

Have previously been treated with:

  1. lapatinib within 12 months of starting study treatment or
  2. neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor(EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously

Have previously been treated with capecitabine for metastatic disease. Note: Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.

Have clinically significant cardiac disease

Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

Are known to be positive for human immunodeficiency virus (HIV)

Unable for any reason to undergo MRI of the brain

CNS Exclusion - Based on screening brain MRI, patients must not have any of the following:

Any untreated brain metastases> 2.0 cm in size, unless discussed with medical monitor

Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of> 2 mg of dexamethasone (or equivalent)

Any lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening MRI may still be eligible for the study based on criteria described under CNS inclusion criteria

Known or concurrent leptomeningeal disease (LMD)

Locations

  • Kaiser Permanente accepting new patients
    Vallejo, California, 94589, United States
  • University of California, Los Angeles accepting new patients
    Los Angeles, California, 90095, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Cascadian Therapeutics Inc.
ID
NCT02614794
Phase
Phase 2
Lead Scientist
Amy Chien
Study Type
Interventional
Last Updated
March 1, 2017
I'm interested in this study!