A Study of Tucatinib (ONT-380) Combined With Capecitabine and/or Trastuzumab in Patients With HER2+ Metastatic Breast Cancer

NCT02025192 | Completed Phase 1 DMC

• 1 other identifier: ONT-380-005
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine the maximal tolerated dose (MTD) or recommended phase 2 dose (RP2D) of tucatinib (ONT-380) and to assess the safety and tolerability of tucatinib (ONT-380) combined with capecitabine alone, trastuzumab alone and with both capecitabine and trastuzumab in patients with HER2+ metastatic breast cancer.

Conditions

HER2 Positive Metastatic Breast Cancers

Keywords

ONT-380; Capecitabine; Trastuzumab; Xeloda; Herceptin; HER2 positive breast cancer; Breast cancer; ARRY-380; Tucatinib

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Up to approximately 4 years

• Severity of adverse events

  Up to approximately 4 years

Secondary Outcomes (11)

• Incidence of clinical lab abnormalities (hematology, chemistry, liver function tests, coagulation, urinalysis)

  Up to approximately 4 years

• Severity of clinical lab abnormalities (hematology, chemistry, liver function tests, coagulation, urinalysis)

  Up to approximately 4 years

• Frequency of dose reductions in tucatinib (ONT-380

  Up to approximately 4 years

• Frequency of dose reductions in capecitabine

  Up to approximately 4 years

• Plasma concentrations of tucatinib (ONT-380) and metabolite

  26 months

Study Arms (3)

Tucatinib (ONT-380) in combination with capecitabine

EXPERIMENTAL

Drug: Tucatinib; Drug: Capecitabine

Tucatinib (ONT-380) in combination with trastuzumab

EXPERIMENTAL

Drug: Tucatinib; Drug: Trastuzumab

Tucatinib (ONT-380) combined with capecitabine and trastuzumab

EXPERIMENTAL

Drug: Tucatinib; Drug: Capecitabine; Drug: Trastuzumab

Interventions

Tucatinib DRUG

Administered twice per day, orally.

Also known as: ONT-380

Tucatinib (ONT-380) combined with capecitabine and trastuzumab; Tucatinib (ONT-380) in combination with capecitabine; Tucatinib (ONT-380) in combination with trastuzumab

Capecitabine DRUG

1000mg/m\^2 administered twice per day, orally in Days 1-14 of each 21-day cycle.

Also known as: Xeloda

Tucatinib (ONT-380) combined with capecitabine and trastuzumab; Tucatinib (ONT-380) in combination with capecitabine

Trastuzumab DRUG

Administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg once every 21 days.

Also known as: Herceptin

Tucatinib (ONT-380) combined with capecitabine and trastuzumab; Tucatinib (ONT-380) in combination with trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic breast cancer, documented as HER2+ by fluorescence in situ hybridization (FISH) and/or 3+ staining by immunohistochemistry (IHC).
• Progressive disease, with a history of prior treatment with both trastuzumab and T-DM1 (unless deemed intolerant to or ineligible for T-DM1 by the investigator) 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 ONT-380, capecitabine, or trastuzumab, whichever is longest.
• Must have target or non-target lesions as per Response Evaluation Criteria In Solid Tumors (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 resolved to ≤ Grade 2; and congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence 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), unless a known history of Gilbert's disease
• Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase \[AST/SGOT\] and alanine aminotransferase/serum glutamic pyruvic transaminase \[ALT/SGPT\]) ≤ 2.5 X ULN (\< 5 X ULN if liver metastases are present)

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.
• Previous treatment with any experimental agent within 14 days or five half-lives of study treatment, whichever is greater.
• Previous treatment 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.
• Previous treatment with cumulative dose of doxorubicin \> 360 mg/m2 or previous treatment with another anthracycline with cumulative dose equivalent to \> 360 mg/m2 doxorubicin.
• Previous treatment with:
• Capecitabine for metastatic disease at any time, for patients assigned to cohorts using capecitabine plus ONT-380 (Combination 1) or capecitabine plus trastuzumab plus ONT-380 (Combination 3). However, patients who have previous treatment with capecitabine for metastatic disease are eligible for enrollment into cohorts using trastuzumab plus ONT-380 (Combination 2). Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible to enroll into all cohorts (Combination 1, 2, or 3).
• 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 expansion cohorts: 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 cohorts: Patients with untreated asymptomatic CNS metastases not requiring 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 capecitabine (for patients assigned to Combination 1 or 3 only), trastuzumab (for patients assigned to Combination 2 or 3 only), or 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.

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (5)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

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: 39368039 DERIVED

• Murthy R, Borges VF, Conlin A, Chaves J, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Jul;19(7):880-888. doi: 10.1016/S1470-2045(18)30256-0. Epub 2018 May 24.

  PMID: 29804905 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinib; Capecitabine; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 31, 2013
• Study Start: December 31, 2013
• Primary Completion: October 3, 2017
• Study Completion: March 16, 2020
• Last Updated: June 4, 2020

Record last verified: 2020-06

Locations

US (5)