Overview

This trial is active, not recruiting.

Conditions her-2 positive breast cancer, metastatic malignant neoplasm to brain
Treatment tesevatinib in combination with trastuzumab
Phase phase 1/phase 2
Targets HER2, VEGF, EGFR, HER, EphB4
Sponsor Kadmon Corporation, LLC
Start date May 2014
End date December 2016
Trial size 80 participants
Trial identifier NCT02154529, KD019-204

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019
(Experimental)
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.
tesevatinib in combination with trastuzumab KD019

Primary Outcomes

Measure
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability and MTD
time frame: 27 months

Secondary Outcomes

Measure
Response Rate
time frame: 27 months
Pharmacokinetics
time frame: 27 months
Median Progression-Free Survival
time frame: 27 months
Median Overall Survival
time frame: 30 months

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

Official title A Phase 1b/2a Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Kadmon Corporation, LLC.