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Trial record 1 of 1 for:    NCT03975647
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A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer

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ClinicalTrials.gov Identifier: NCT03975647
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : September 21, 2021
Sponsor:
Information provided by (Responsible Party):
Seagen Inc.

Tracking Information
First Submitted Date  ICMJE June 4, 2019
First Posted Date  ICMJE June 5, 2019
Last Update Posted Date September 21, 2021
Actual Study Start Date  ICMJE October 2, 2019
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2019)
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment [ Time Frame: Up to approximately 5 years ]
PFS per investigator is defined as the time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2019)
  • Overall Survival [ Time Frame: Up to approximately 5 years ]
    OS is defined as the time from randomization to death due to any cause.
  • PFS per RECIST v1.1 by blinded independent committee review (BICR) [ Time Frame: Up to approximately 5 years ]
    PFS per BICR is defined as the time from the date of randomization to the centrally-reviewed documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
  • PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]
  • PFS per RECIST v1.1 by BICR in patients with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]
  • Objective response rate (ORR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
    ORR is defined as the proportion of subjects with complete response (CR) or partial response (PR) according to RECIST v1.1.
  • ORR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
  • Duration of response (DOR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 5 years ]
    DOR is defined as the time from first documentation of objective response to the first documentation of disease progression or death from any cause, whichever occurs earlier.
  • DOR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 5 years ]
  • Clinical benefit rate (CBR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
    CBR is defined as the proportion of subjects with stable disease (SD) or non-CR or non-PD for ≥6 months or best response of CR or PR according to RECIST v1.1.
  • CBR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
  • Number of participants with adverse events (AEs) [ Time Frame: Through 1 month following last dose; up to approximately 9 months overall per participant ]
    An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
Official Title  ICMJE Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)
Brief Summary

This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery.

Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer.

Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.

Detailed Description

This study is designed to evaluate the efficacy and safety of tucatinib in combination with T-DM1 in subjects with unresectable locally-advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane and trastuzumab in any setting. Prior pertuzumab treatment is permitted, but not required. Subjects will be randomized in a 1:1 manner to receive 21-day cycles of either tucatinib or placebo in combination with T-DM1.

While on study treatment, subjects will be assessed for progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions. Study treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. After completion of study treatment and after occurrence of disease progression, subjects in both arms of the study will continue to be followed for survival until study closure or withdrawal of consent.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE HER2-positive Breast Cancer
Intervention  ICMJE
  • Drug: tucatinib
    300mg given twice per day by mouth (orally)
    Other Name: ONT-380
  • Drug: placebo
    Given twice per day orally
  • Drug: T-DM1
    3.6 mg/kg given into the vein (IV; intravenously) every 21 days
    Other Name: Kadcyla
Study Arms  ICMJE
  • Experimental: Tucatinib + T-DM1
    Tucatinib + T-DM1
    Interventions:
    • Drug: tucatinib
    • Drug: T-DM1
  • Active Comparator: Placebo + T-DM1
    Placebo + T-DM1
    Interventions:
    • Drug: placebo
    • Drug: T-DM1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 4, 2019)
460
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2024
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • Inclusion Criteria:

    • Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory
    • History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination
    • Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy
    • Measurable or non-measurable disease assessable by RECIST v1.1
    • ECOG performance status score of 0 or 1
    • CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), subjects must have at least one of the following:

      (a) No evidence of brain metastases

      (b) Untreated brain metastases not needing immediate local therapy

      (c) 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, provided that there is no clinical indication for immediate re-treatment with local therapy
      2. Subjects treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met:

        (i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 21 days prior to first dose, or time since surgical resection is at least 28 days.

        (ii) Other sites of evaluable disease are present

      3. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
  • Exclusion Criteria:

    • Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity).
    • CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), subjects must not have any of the following:

      1. Any untreated brain lesions >2 cm in size
      2. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).
      3. Any brain lesion thought to require immediate local therapy
      4. Known or concurrent leptomeningeal disease as documented by the investigator
      5. Poorly controlled generalized or complex partial seizures
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Denmark,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03975647
Other Study ID Numbers  ICMJE SGNTUC-016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Seagen Inc.
Study Sponsor  ICMJE Seagen Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Evelyn Rustia, MD Seagen Inc.
PRS Account Seagen Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP