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A Study of Tucatinib vs. Placebo in Combination With 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 : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Seattle Genetics, Inc.

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.


Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Drug: tucatinib Drug: placebo Drug: T-DM1 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 460 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Tucatinib + T-DM1 Drug: tucatinib
300mg given twice per day orally

Drug: T-DM1
3.6 mg/kg given intravenously every 21 days

Active Comparator: Placebo + T-DM1 Drug: placebo
Given twice per day orally

Drug: T-DM1
3.6 mg/kg given intravenously every 21 days




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to approximately 5 years ]
    OS is defined as the time from randomization to death due to any cause.

  2. 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.

  3. PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]
  4. PFS per RECIST v1.1 by BICR in patients with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]
  5. 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.

  6. ORR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
  7. 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.

  8. DOR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 5 years ]
  9. 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.

  10. CBR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
  11. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

    • Histologically confirmed HER2+ metastatic 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 LA/M breast cancer after last systemic therapy, or be intolerant of last systemic therapy
    • Measureable or non-measurable disease assessable by RECIST v1.1
    • ECOG performance status score of 0 or 1
    • Life expectancy ≥6 months
    • 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 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, lapatinib, neratinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent
    • Prior treatment with T-DM1
    • Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, experimental agent or participation in another interventional clinical trial ≤3 weeks prior to first dose of study treatment
    • Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:

      1. Alopecia;
      2. Neuropathy, which must have resolved to ≤ Grade 2;
      3. Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely
    • Clinically significant cardiopulmonary disease
    • Myocardial infarction or unstable angina within 6 months prior to first dose of study treatment
    • Carrier of Hepatitis A or Hepatitis C or has other known chronic liver disease
    • Positive for human immunodeficiency virus (HIV)
    • Subjects who are pregnant, breastfeeding, or planning to become pregnant from time of informed consent until 7 months following the last dose of study drug
    • Unable to swallow pills or has significant gastrointestinal disease which would preclude the adequate oral absorption of medications
    • Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment
    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975647


Contacts
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Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
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United States, Nebraska
Nebraska Cancer Specialists Recruiting
Omaha, Nebraska, United States, 68130
Contact: Marsha Ketcham    402-884-7857    mketcham@nebraskacancer.com   
Principal Investigator: Margaret Block, M.D.         
Sponsors and Collaborators
Seattle Genetics, Inc.
Investigators
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Study Director: Evelyn Rustia, MD Seattle Genetics, Inc.

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Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT03975647     History of Changes
Other Study ID Numbers: SGNTUC-016
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 8, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Ado-trastuzumab emtansine
Maytansine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action