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A Study of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer | Clinical Trials | Clareo Health

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A Study of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (Trastuzumab Emtansine; T-DM1)

NCT01983501•Seagen Inc.

View on ClinicalTrials.gov

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.

Detailed Description

This is a Phase 1b, open-label study of tucatinib (ONT-380) given in combination with ado-trastuzumab emtansine (T-DM1) to patients with HER2+ breast cancer. This study will use a 3+3 dose escalation design to evaluate up to four dose levels of tucatinib ONT-380 in order to identify the maximal tolerated dose/recommended dose (MTD/RD) of tucatinib (ONT-380) in combination with T-DM1. T-DM1 will be administered intravenously on day 1 of each cycle (except cycle 1, when it will be administered on day 2 to allow for PK assessments of tucatinib (ONT-380) alone).Tucatinib (ONT-380) will be administered orally, twice per day on days 1-21 of each cycle. There will be 3-6 evaluable patients enrolled in each cohort in the dose escalation phase, unless that dose is found to be intolerable prior to completion of enrollment. At least 6 evaluable patients are to be treated at a dose level in order for an MTD/RD to be declared. Once an MTD/RD is declared, an additional 24 evaluable patients will be in enrolled in a MTD/RD expansion cohort for a total of 30 evaluable patients to be treated at the MTD/RD. In addition to the MTD/RD expansion cohort, an optional additional cohort of up to 15 evaluable patients with either untreated, asymptomatic CNS metastases not needing immediate local therapy or progressive CNS metastasis following local therapy may also be enrolled and treated at the MTD/RD. Up to 63 evaluable patients may be treated in this study.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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:
+9 more criteria

Exclusion Criteria

•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.
+11 more criteria

Locations (11)

University of Alabama

Birmingham, Alabama, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

University of Kansas

Kansas City, Kansas, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Providence Cancer Center

Portland, Oregon, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Northwest Medical Specialties

Tacoma, Washington, United States

London Health Sciences Centre

London, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Hospital de la Cite-de-la-Sante

Laval, Quebec, Canada

Key Dates

Start Date

February 28, 2014

Primary Completion Date

October 10, 2017

Completion Date

September 3, 2020

Last Updated

September 21, 2020

Enrollment

ACTUAL participants

Conditions

HER2 Positive Breast Cancers

Interventions

Tucatinib (ONT-380)

DRUG

T-DM1

DRUG