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Trial record 1 of 1 for:    NCT02614794
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Phase 2 Study of Tucatinib vs Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer (HER2CLIMB)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Cascadian Therapeutics Inc.
Sponsor:
Information provided by (Responsible Party):
Cascadian Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT02614794
First received: November 20, 2015
Last updated: April 4, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
HER2 Positive Breast Cancer
Drug: Tucatinib
Drug: Capecitabine
Drug: Trastuzumab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Cascadian Therapeutics Inc.:

Primary Outcome Measures:
  • Progression-free survival (PFS) per RECIST 1.1 based on independent central review [ Time Frame: 42 months ]

Secondary Outcome Measures:
  • Effect of tucatinib in combination with capecitabine and trastuzumab on overall survival (OS) [ Time Frame: 52 months ]
  • Progression-free survival (PFS) in the subgroup of patients with baseline brain metastases per RECIST 1.1 based on central review [ Time Frame: 42 months ]

Estimated Enrollment: 480
Study Start Date: December 2015
Estimated Study Completion Date: January 2021
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tucatinib in combination with capecitabine & trastuzumab
Tucatinib in combination with capecitabine & trastuzumab
Drug: Tucatinib
Treatment will be administered in cycles of 21 days each. Tucatinib 300 mg or placebo will be given orally twice daily (PO BID). Capecitabine will be given at 1000 mg/m2 PO BID on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV) followed by 6 mg/kg once every 21 days.
Other Name: ONT-380
Drug: Capecitabine
Treatment will be administered in cycles of 21 days each. Tucatinib 300 mg or placebo will be given orally twice daily (PO BID). Capecitabine will be given at 1000 mg/m2 PO BID on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV) followed by 6 mg/kg once every 21 days.
Other Name: Xeloda
Drug: Trastuzumab
Treatment will be administered in cycles of 21 days each. Tucatinib 300 mg or placebo will be given orally twice daily (PO BID). Capecitabine will be given at 1000 mg/m2 PO BID on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV) followed by 6 mg/kg once every 21 days.
Other Name: Herceptin
Active Comparator: Placebo in combination with capecitabine & trastuzumab
Placebo in combination with capecitabine & trastuzumab
Drug: Capecitabine
Treatment will be administered in cycles of 21 days each. Tucatinib 300 mg or placebo will be given orally twice daily (PO BID). Capecitabine will be given at 1000 mg/m2 PO BID on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV) followed by 6 mg/kg once every 21 days.
Other Name: Xeloda
Drug: Trastuzumab
Treatment will be administered in cycles of 21 days each. Tucatinib 300 mg or placebo will be given orally twice daily (PO BID). Capecitabine will be given at 1000 mg/m2 PO BID on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV) followed by 6 mg/kg once every 21 days.
Other Name: Herceptin
Drug: Placebo
Treatment will be administered in cycles of 21 days each. Tucatinib 300 mg or placebo will be given orally twice daily (PO BID). Capecitabine will be given at 1000 mg/m2 PO BID on Days 1-14 of each 21-day cycle. Trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV) followed by 6 mg/kg once every 21 days.

Detailed Description:

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.

  Eligibility

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

Inclusion Criteria

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

Exclusion Criteria

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)

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02614794

  Show 62 Study Locations
Sponsors and Collaborators
Cascadian Therapeutics Inc.
Investigators
Study Director: Luke Walker, MD Cascadian Therapeutics Inc.
  More Information

Responsible Party: Cascadian Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02614794     History of Changes
Other Study ID Numbers: ONT-380-206
Study First Received: November 20, 2015
Last Updated: April 4, 2017

Keywords provided by Cascadian Therapeutics Inc.:
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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Capecitabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017