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Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

This study has been terminated.
(Sponsor closed the study in order to review data from other ongoing tesevatinib oncology studies, and to determine feasibility of continuing this study)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02154529
First Posted: June 3, 2014
Last Update Posted: August 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Kadmon Corporation, LLC
  Purpose
Evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) of the combination of tesevatinib and trastuzumab in subjects with HER2-positive metastatic breast cancer

Condition Intervention Phase
HER-2 Positive Breast Cancer Metastatic Malignant Neoplasm to Brain Drug: Tesevatinib in combination with Trastuzumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Kadmon Corporation, LLC:

Primary Outcome Measures:
  • Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability and MTD [ Time Frame: 27 months ]
    To evaluate the safety and tolerability and determine the MTD of the combination of tesevatinib and trastuzumab in subjects with HER2-positive metastatic breast cancer.


Secondary Outcome Measures:
  • Response Rate [ Time Frame: 27 months ]
    To determine the response rate (RR) using RECIST for non-CNS disease and by the Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases.

  • Pharmacokinetics [ Time Frame: 27 months ]
    To evaluate the following pharmacokinetic parameters (Cmax, Tmax, and AUC[0-24hr]) for the combination of tesevatinib and trastuzumab. Plasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug.

  • Median Progression-Free Survival [ Time Frame: 27 months ]
    To determine the median progression-free survival (PFS) and the percentage of subjects without disease progression after 2, 4, and 6 months of dosing.

  • Median Overall Survival [ Time Frame: 30 months ]
    To determine the median overall survival (OS).


Other Outcome Measures:
  • Neurologic Symptoms [ Time Frame: 12 months ]
    To evaluate changes in neurologic symptoms in subjects with leptomeningeal metastases. This outcome measure is specific to subjects with leptomeningeal metastases (Phase 2a, Group 3).

  • Clearance of Cerebrospinal Fluid Cytology [ Time Frame: 12 months ]
    To evaluate clearance of cerebrospinal fluid (CSF) cytology in subjects with leptomeningeal metastases. This outcome measure is specific to subjects with leptomeningeal metastases (Phase 2a, Group 3).


Enrollment: 17
Study Start Date: May 2014
Study Completion Date: November 9, 2015
Primary Completion Date: November 9, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b, Arm 1
Tesevatinib in combination with Trastuzumab. Tesevatinib will be orally administered to subjects at 150mg once daily in combination with Trastuzumab 8mg/kg every 3 weeks.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 1b, Arm 2
Tesevatinib in combination with Trastuzumab. Tesevatinib will be orally administered to subjects at 250mg once daily in combination with Trastuzumab 8mg/kg every 3 weeks.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 1b, Arm 3
Tesevatinib in combination with Trastuzumab. Tesevatinib will be orally administered to subjects at 300mg once daily in combination with Trastuzumab 8mg/kg every 3 weeks.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 1b, Arm 4
Tesevatinib in combination with Trastuzumab. Tesevatinib will be orally administered to subjects at 350mg once daily in combination with Trastuzumab 8mg/kg every 3 weeks.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 1b, Arm 5
Tesevatinib in combination with Trastuzumab. Tesevatinib will be orally administered to subjects at 400mg once daily in combination with Trastuzumab 8mg/kg every 3 weeks.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 2a, Group 1
Tesevatinib in combination with Trastuzumab. In the Phase 2a expansion group, tesevatinib will be orally administered to all subjects once daily at the MTD dose determined in Phase 1b in combination with Trastuzumab 8mg/kg every 3 weeks. Subjects will include those with HER2-positive breast cancer and brain metastases that have progressed after radiation therapy.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 2a, Group 2
Tesevatinib in combination with Trastuzumab. In the Phase 2a expansion group, tesevatinib will be orally administered to all subjects once daily at the MTD dose determined in Phase 1b in combination with Trastuzumab 8mg/kg every 3 weeks. Subjects will include those with HER2-positive metastatic breast cancer who do not have brain metastases, or who have asymptomatic brain metastases, or who have minimally symptomatic brain metastases that do not require immediate radiation therapy or neurosurgery.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin
Experimental: Phase 2a, Group 3
Tesevatinib in combination with Trastuzumab. In the Phase 2a expansion group, tesevatinib will be orally administered to all subjects once daily at the MTD dose determined in Phase 1b in combination with Trastuzumab 8mg/kg every 3 weeks. Subjects will be limited to those with HER2-positive metastatic breast cancer with pathologically confirmed leptomeningeal metastases with or without brain metastases. Brain metastases do not have to have progressed after radiation therapy in this group.
Drug: Tesevatinib in combination with Trastuzumab
Other Names:
  • KD019
  • XL647
  • Herceptin

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Females with histologically or cytologically confirmed HER2-positive breast cancer. HER2-positive is defined as 3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization or silver in situ hybridization with HER2/CEP17 ratio ≥ 2.0
  • Metastatic disease that has progressed on previous therapy or previous therapy was not tolerated
  • Subjects in the Phase 1b portion and in Group 1 and Group 3 of the Phase 2a portion may have received any number of prior therapies for breast cancer. Subjects in Group 2 of the Phase 2a portion may have received up to 3 lines of therapy in the metastatic setting (not including adjuvant or neoadjuvant therapy)

    • Must have included trastuzumab, pertuzumab, and trastuzumab emtansine. Subjects starting initial systemic therapy for HER2-positive breast cancer prior to June 2012 are not required to have had pertuzumab
    • If the subject has ER+ breast cancer, prior therapy must have included at least 1 hormonal therapy
    • Subjects with asymptomatic brain metastases found on screening MRI may be entered into Phase 1b or into Group 2 of the Phase 2a without prior radiation therapy to the brain. Subjects with minimally symptomatic brain metastases found on screening MRI may be entered into Phase 1b or into Group 2 of the Phase 2a without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy
    • Subjects with leptomeningeal metastases may or may not have brain metastases. When brain metastases are present, they do not need to have progressed after radiation therapy
  • At least 1 measurable breast cancer lesion that is ≥ 10mm in one dimension (or ≥15mm in shortest axis for lymph nodes) by spiral CT scan or by brain MRI

    • Subjects in Group 3 are not required to have measurable disease but must have cytologic confirmation of leptomeningeal disease
  • No increase in steroid dose during the week prior to screening brain MRI
  • No history of another malignancy in the past 5 years, except treated non-melanoma skin cancer or superficial bladder cancer or carcinoma-in-situ of the cervix
  • Adequate organ and bone marrow functions
  • Serum potassium and magnesium levels within normal limits
  • Cardiac ejection fraction within normal limits as measured by echocardiogram
  • Women of childbearing potential must have negative urine pregnancy test. Sexually active women must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes IUD plus one barrier method; on stable doses of hormonal contraception for at least 3 months plus one barrier method; 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides; or vasectomized partner

Key Exclusion Criteria:

  • CSF cytology positive for malignant cells or symptomatic leptomeningeal carcinomatosis in the Phase 1b portion. In Group 3, subjects are required to have CSF cytology positive for malignant cells
  • Taking any medication known to inhibit the CYP3A4 isozyme or any drugs that are CYP3A4 inducers (including phenytoin), or any drugs associated with torsades de pointes or known to prolong the QTc(f) interval within 2 weeks prior to Day 1 of treatment on study. A stable regimen of antidepressants of the SSRI class is allowed
  • Evidence of active heart disease within the 3 months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction, torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia, heart block, or congenital long QT syndrome
  • Has an active infectious process
  • Has marked prolongation of QTc interval at screening or baseline using the Fridericia method of correction for heart rate
  • History of gastrointestinal condition that might interfere with drug absorption
  Contacts and Locations
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): NCT02154529


Locations
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
United States, Indiana
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New Mexico
San Juan Oncology
Farmington, New Mexico, United States, 87401
United States, New York
Laura and Isaac Perlmutter Cancer Center @ NYU Langone
New York, New York, United States, 10016
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Kadmon Corporation, LLC
  More Information

Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT02154529     History of Changes
Other Study ID Numbers: KD019-204
First Submitted: May 28, 2014
First Posted: June 3, 2014
Last Update Posted: August 30, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Trastuzumab
Antineoplastic Agents