NCT01983501

Brief Summary

The purpose of this study is to determine the maximal tolerated dose (MTD) or recommended dose (RD) and to assess the safety and tolerability of tucatinib (ONT-380) combined with ado-trastuzumab emtansine (T-DM1) in patients with HER2+ breast cancer.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Feb 2014

Longer than P75 for phase_1

Geographic Reach
2 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 28, 2013

Completed
17 days until next milestone

First Posted

Study publicly available on registry

November 14, 2013

Completed
4 months until next milestone

Study Start

First participant enrolled

February 28, 2014

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 10, 2017

Completed
2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 3, 2020

Completed
Last Updated

September 21, 2020

Status Verified

September 1, 2020

Enrollment Period

3.6 years

First QC Date

October 28, 2013

Last Update Submit

September 17, 2020

Conditions

HER2 Positive Breast Cancers

Keywords

ONT-380T-DM1KadcylaBreast cancerARRY-380Tucatinib

Outcome Measures

Primary Outcomes (1)

  • Incidence of adverse events

    12 months

Secondary Outcomes (8)

  • Incidence of clinical lab abnormalities

    12 months

  • Frequency of dose reductions in tucatinib

    12 months

  • Frequency of dose reductions in T-DM1

    12 months

  • Objective response rate (ORR)

    12 months

  • Duration of response

    12 months

  • +3 more secondary outcomes

Study Arms (1)

Tucatinib (ONT-380) in combination with T-DM1

EXPERIMENTAL
Drug: Tucatinib (ONT-380)Drug: T-DM1

Interventions

Tucatinib (ONT-380)DRUG

Given twice per day, orally

Tucatinib (ONT-380) in combination with T-DM1
T-DM1DRUG

Given intravenously once every 21 days

Also known as: Kadcyla
Tucatinib (ONT-380) in combination with T-DM1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HER2+ metastatic breast cancer, documented as HER2+ by FISH and/or 3+ staining by immunohistochemistry.
  • History of prior therapy with trastuzumab and a taxane, separately or in combination. For patients in dose escalation and MTD expansion cohorts, prior therapy with trastuzumab and a taxane must have been for metastatic disease. For patients in CNS disease expansion cohorts, trastuzumab and taxane (together or separately) may have been given at any time prior to study enrollment as part of neoadjuvant therapy, adjuvant therapy, or therapy for metastatic disease.
  • If female and of child-bearing potential, has negative pregnancy test within 14 days prior to treatment.
  • If a sexually active male or a sexually active female of child-bearing potential, agrees to use dual (two concurrent) forms of medically accepted contraception from the time of consent until 6 months after the last dose of either tucatinib (ONT-380) or T-DM1, whichever is longer.
  • Signed an informed consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC).
  • Must have target or non-target lesions as per RECIST 1.1.
  • All toxicity related to prior cancer therapies must have resolved to ≤ Grade 1, with the following exceptions: alopecia; neuropathy, which must have to resolved to ≤ Grade 2; and congestive heart failure (CHF), which must have been ≤ Grade 1 in severity and must have resolved completely.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
  • In the opinion of the Investigator, life expectancy \> 6 months.
  • Adequate hematologic function as defined by:
  • Hemoglobin ≥ 9 g/dL
  • Absolute neutrophil count (ANC) ≥ 1000 cells/µL
  • Platelets ≥ 100,000/µL
  • Adequate hepatic function as defined by the following:
  • Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
  • +4 more criteria

You may not qualify if:

  • Medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures.
  • Patient is breastfeeding.
  • Patient was treated with any experimental agent within 14 days or five half-lives of study treatment, whichever is greater.
  • Patient was treated with trastuzumab or other antibody based therapy within three weeks of starting study treatment or with chemotherapy or hormonal cancer therapy within two weeks of starting study treatment.
  • Patient had prior exposure to a cumulative dose of doxorubicin that exceeded 360 mg/m2 or its equivalent.
  • Previous treatment with T-DM1 at any time; or previous treatment with any small molecule HER2 inhibitors including (but not limited to) lapatinib, neratinib, or afatinib within the last 4 weeks prior to initiation of study therapy.
  • CNS disease:
  • Patients with leptomeningeal disease are excluded
  • Dose escalation and MTD/RP2D expansion cohort: Patients with symptomatic CNS metastases are excluded. Patients with treated CNS metastases or untreated asymptomatic CNS metastases not requiring immediate local therapy may be eligible. Enrollment of patients with metastases must be approved by the study medical monitor.
  • Optional CNS disease expansion cohort: Patients with asymptomatic untreated CNS metastases not needing immediate local therapy or patients with progressive CNS disease following local therapy may be eligible with medical monitor approval.
  • History of allergic reactions to compounds of similar chemical or biological composition to T-DM1 or tucatinib (ONT-380), except for a history of Grade 1 or Grade 2 Infusion Related Reaction to trastuzumab which has been successfully managed.
  • Patients with uncorrectable electrolyte abnormalities.
  • Known to be HIV positive. HIV testing is not required for those patients who are not known to be positive.
  • Known carrier of Hepatitis B and / or Hepatitis C (whether active disease or not).
  • Known liver disease, autoimmune hepatitis, or sclerosing cholangitis.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98045, United States

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5T 2M9, Canada

Location

Hospital de la Cite-de-la-Sante

Laval, Quebec, H7M 3L9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (2)

  • Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5.

    PMID: 39368039DERIVED

  • Borges VF, Ferrario C, Aucoin N, Falkson C, Khan Q, Krop I, Welch S, Conlin A, Chaves J, Bedard PL, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncol. 2018 Sep 1;4(9):1214-1220. doi: 10.1001/jamaoncol.2018.1812.

    PMID: 29955792DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinibAdo-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

MaytansineMacrolidesLactonesOrganic ChemicalsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsTrastuzumabAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • JoAl Mayor, PharmD, BCOP

    Seagen Inc.

    STUDY DIRECTOR

  • Corinna Palanca-Wessels, MD, PhD

    Seagen Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 28, 2013

First Posted

November 14, 2013

Study Start

February 28, 2014

Primary Completion

October 10, 2017

Study Completion

September 3, 2020

Last Updated

September 21, 2020

Record last verified: 2020-09

Locations

US(7)CA(4)