HER-2 Positive Breast CancerPhase 1/2NCT02154529
Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer
A Phase 1/2 study testing Tesevatinib and Trastuzumab in people with HER-2 Positive Breast Cancer and Metastatic Malignant Neoplasm to Brain, run by Kadmon Corporation, LLC at 6 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HER-2 Positive Breast Cancer, Metastatic Malignant Neoplasm to Brain
- What is being tested?
- Tesevatinib and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 6 sitesUnited States
- Study dates
- May 2014to 13 Sep 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be included if they meet the following criteria:
- Female ≥ 18 years old.
- 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 (FISH) or silver in situ hybridization (SISH) 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 of the study and in Group 1 and Group 3 of the Phase 2a portion of the study may have received any number of prior therapies for breast cancer. Subjects in Group 2 of the Phase 2a portion of the study may have received up to 3 lines of therapy in the metastatic setting (not including adjuvant or neoadjuvant therapy).
- Previous therapies must have included trastuzumab, pertuzumab, and trastuzumab emtansine. However, subjects starting initial systemic therapy for HER2-positive breast cancer prior to June 2012, when pertuzumab was approved for initial treatment of patients with HER2-positive breast cancer, are not required to have had pertuzumab.
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- 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 in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant.
- Subjects with brain metastases that are progressing in the brain after radiation therapy are eligible for enrollment in both Phase 1b and Group 1 of the Phase 2a, provided that there has been no further local therapy for the progressing brain metastases. These subjects must have previously received trastuzumab, pertuzumab (if received initial systemic therapy for HER2-positive breast cancer prior to June 2012 when pertuzumab was approved for initial systemic therapy of HER2-positive, metastatic breast cancer), and trastuzumab emtansine.
- 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.
- Subjects with disease progression in the brain after prior brain radiation therapy may have extra-CNS metastases in any location or may have no extra-CNS metastases.
- At least 1 measurable breast cancer lesion that is ≥ 10 mm in one dimension (or
- ≥ 15 mm in shortest axis for lymph nodes) by spiral CT scan or by brain MRI. All brain metastases should be evaluated by T1-weighted, gadolinium-enhanced magnetic resonance imaging (MRI). Subjects with leptomeningeal metastases (Group 3) are not required to have measurable disease but must have cytologic confirmation of leptomeningeal disease.
- Trastuzumab therapy and hormonal therapy for breast cancer treatment started prior to study entry may be continued. However, previous chemotherapy (including antibodies other than trastuzumab) for breast cancer treatment must have been discontinued at least 14 days before the start of study treatment. Surgical procedures other than port placement must have been performed at least 14 days prior to the start of study treatment. Subjects must have recovered from the reversible effects of prior breast cancer treatments, including surgery and radiation therapy (excluding alopecia).
- No increase in corticosteroid 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.
- ECOG (Eastern Cooperative Oncology Group) status of ≤ 1 (see Appendix C). However, subjects in Group 3 (leptomeningeal metastases) require ECOG status of ≤ 2.
- Adequate organ and bone marrow functions as follows: (a) Serum creatinine ≤ 1.5 mg/dL; (b) total bilirubin ≤ 1.5 × upper limit of normal (ULN); (c) alanine aminotransferase and aspartate aminotransferase ≤ 3× ULN; (d) white blood cell count > 3000/mm^3; (e) absolute neutrophil count ≥ 1500/mm^3; (f) platelet count > 100,000/mm^3; and (g) hemoglobin > 8 g/dL
- Serum potassium and magnesium levels within normal limits (WNL).
- Cardiac ejection fraction WNL as measured by echocardiogram, as long as lower limit of normal (LLN) at the institution is ≥ 50%.
- No coexisting medical problems of sufficient severity to limit compliance with the study.
- Willing and able to sign written informed consent and be able to comply with the study protocol for the duration of the study.
- Women of childbearing potential (ie, menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test). Sexually active women of childbearing potential enrolled in the study must agree to use 2 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: (a) Intrauterine Device (IUD) plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal) plus 1 barrier method; (c) 2 barrier methods where effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner.
Who cannot join
- A subject who meets any of the following criteria is ineligible for entry into the study:
- Any concurrent therapy for breast cancer other than the specified treatment in this study. Concurrent treatment with bisphosphonates or denosumab is allowed, if started prior to the start of tesevatinib administration.
- Cerebrospinal fluid (CSF) cytology positive for malignant cells or symptomatic leptomeningeal carcinomatosis in the Phase 1b portion of the study. Note: In Group 3 of the Phase 2a portion of the study, 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, including anti-arrhythmic medications within 2 weeks prior to Day 1 of treatment in the study. A stable regimen (≥ 4 weeks) of antidepressants of the SSRI(selective serotonin reuptake inhibitor) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine).
- Has evidence of active heart disease such as myocardial infarction within the 3 months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction.
- History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR(partial response) interval only), or congenital long QT syndrome. Subjects with a history of atrial arrhythmias should be discussed with the medical monitor.
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- Has an active infectious process.
- Female subject who is pregnant or lactating.
- Known contraindication to MRI, such as cardiac pacemaker, shrapnel, or ocular foreign body.
- Has had major surgery without full recovery.
- Has marked prolongation of QTc interval at screening or baseline (QTc interval > 470 msec) using the Fridericia method of correction for heart rate.
- History of gastrointestinal (GI) condition that might interfere with drug absorption
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
San Juan Oncology
Farmington, New Mexico, 87401
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Laura and Isaac Perlmutter Cancer Center @ NYU Langone
New York, New York, 10016
About this study
Official title: A Phase 1b/2a Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer
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
Read the detailed description
This is a multicenter, Phase 1b/2a, multiple ascending-dose, open-label study designed to assess the safety, tolerability, and efficacy of tesevatinib (KD019) in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study planned to include a Phase 2a expansion in which approximately 50 subjects would receive tesevatinib at the maximum tolerated dose (MTD) dose determined in Phase 1b.
The study employs a successive cohort dose-escalation designed to determine the MTD of tesevatinib in combination with trastuzumab. The MTD dose is defined as the dose level below in which : (a) 2 of 3 subjects (or 2 of 6 subjects if Grade ≥ 3 tesevatinib related treatment emergent adverse event [TEAE] experience in 1 of the first 3 subjects).
In the Phase 1b portion of the study, tesevatinib is to be administered orally (PO) to successive cohorts of subjects at 150 mg, 250 mg, 300 mg, 350 mg, and 400 mg once daily (QD).
The following 4 dossing cohorts are initiated during the study:
- Cohort 1: 150 mg tesevatinib PO QD
- Cohort 2: 250 mg tesevatinib PO QD
- Cohort 3: 300 mg tesevatinib PO QD
- Cohort 4: 350 mg tesevatinib PO QD
[Note: the sponsor suspended the study before a cohort of subjects were enrolled at tesevatinib 400 mg PO QD.]
Trastuzumab is administered intravenously (IV) at 8 mg/kg as an initial loading dose on Day 1 of Cycle 1, followed by 6 mg/kg IV every 3 weeks thereafter, beginning Day 1 of Cycle 2. Subjects entering the study already on trastuzumab are not to receive the initial loading dose and instead receive trastuzumab 6 mg/kg IV. The first doses of trastuzumab and tesevatinib are administered in the clinic on Study Day 1. Subsequent doses of tesevatinib are to be taken on an outpatient basis for the remainder of each 21-day cycle. During Cycle 1, subjects are to be returned to the clinic for weekly safety and tolerability assessments.
Tumor response, both in the central nervous system (CNS) and peripheral to the CNS, is to be assessed after the second cycle of treatment and then at the end of every 2 cycles of treatment thereafter. Subjects are to be treated until disease progression or the subject experienced unacceptable toxicity. Subjects who demonstrated tumor progression are to stop study drug and followed for survival. All subjects discontinuing tesevatinib therapy are to be followed for survival.
Safety assessments include adverse event monitoring, electrocardiograms (ECGs), laboratory testing, physical examinations, vital signs, and pregnancy testing.
An End-of-Treatment visit is to be conducted as soon as possible after the subject's last dose of study drug. This could occur at the visit when disease progression is diagnosed. Subjects are to be followed for disease progression and survival.
A follow-up visit planned for 30 days (± 5 days) after the last dose of study drug assessments is to include collection of AE (Adverse Event) and concomitant medication data. This visit could occur prior to 30 days if a new therapy is started within 30 days of last dose of study drug.
For long-term follow-up, subjects are to be contacted by telephone every 8 weeks to assess survival status and any subsequent anti-cancer treatment.
The duration of treatment for subjects with tesevatinib in combination with trastuzumab is planned until the subject experiences disease progression or unacceptable toxicity.
[Note: Changes to the Planned Analysis: The study, planned to include a Phase 2a expansion in which approximately 50 subjects would have received tesevatinib at the MTD dose determined in Phase 1b, was terminated early. Although some patients had prolonged stable disease in the study, no clear treatment responses were observed. The sponsor decided to suspend the study while gathering additional data from other tesevatinib oncology studies. The study was subsequently terminated early because the sponsor stopped evaluations of tesevatinib as a treatment for HER2-positive metastatic breast cancer.]
- Being tested
- Tesevatinib, Trastuzumab
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TesevatinibDrug
Also called KD019, XL647
TrastuzumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Tesevatinib in combination with Trastuzumab: tesevatinib 150 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. Receives: Drug: Tesevatinib; Drug: Trastuzumab |
| Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Tesevatinib in combination with Trastuzumab: tesevatinib 250 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. Receives: Drug: Tesevatinib; Drug: Trastuzumab |
| Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Tesevatinib in combination with Trastuzumab: tesevatinib 300 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. Receives: Drug: Tesevatinib; Drug: Trastuzumab |
| Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Tesevatinib in combination with Trastuzumab: tesevatinib 350 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. Receives: Drug: Tesevatinib; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) by Severity and/or Relationship to Tesevatinib
Percentage of subjects with at least 1 treatment-emergent adverse event of Grade 3 or greater or relationship with tesevatinib. TEAE grading was by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) where Grade 3 is severe and Grade 4 is life-threatening. TEAEs were considered related to study drug if the investigator assessed them as possibly related, probably related, or related.
Measured: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up
Safety and Tolerability: Percentage of Subjects With Serious Adverse Event (SAE) Related to Tesevatinib
Percentage of subjects with at least 1 serious adverse event considered related to study drug. SAEs were considered related to tesevatinib drug if the investigator assessed them as possibly related, probably related, or related.
Measured: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up
Secondary outcomes (5)
Pharmacokinetics (PK): Mean Serum Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
The mean of the maximum serum concentration (Cmax) for the combination of tesevatinib and trastuzumab after 1 cycle (Cycle 2 Day 1).
Measured: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Median Serum Tmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
The median time of the maximum serum concentration (Tmax) for the combination of tesevatinib and trastuzumab after 1 cycle (Cycle 2 Day 1)
Measured: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Mean Serum AUC(0-t) (Area Under Curve) of Treatment With Tesevatinib + Trastuzumab
The mean area under the concentration-time curve during the period from 0 to a given time point 't' in the tesevatinib 150 mg QD, 250 mg QD, and 300 mg QD cohorts.
Measured: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Mean AR Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
The mean of the arithmetic mean accumulation ratio (AR) of the maximum concentration of tesevatinib. The AR is defined as:
Cmax for Cycle 2 divided by Cmax of Cycle 1.
Measured: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Mean AR AUC(0-24hr) After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
The mean of the arithmetic mean accumulation ratio (AR) of the area under the concentration-time curve from 0 to 24 hours. The AR is defined as:
AUC(0-24hr) for Cycle 2 divided by AUC(0-24hr) for Cycle 1.
Measured: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2014 (estimated)
- Study startMay 2014
- Primary completion13 Sep 2015
- Study completion13 Sep 2015
Why it stopped: Sponsor closed the study due to lack of response.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HER-2 Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A phase 1b ascending dose-finding study for establishing the maximum tolerated dose (MTD) of tesevatinib (with trastuzumab).
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kadmon Corporation, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02154529
- Sponsor's protocol ID
- KD019-204
- Status last verified
- Apr 2022
- First submitted
- 28 May 2014
- Last updated
- 27 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT02154529
- Acronym / sponsor ID
- KD019-204
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor closed the study due to lack of response.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Kadmon Corporation, LLCIndustry (pharma, biotech, devices)
- Study start
- May 2014
- Primary completion
- 13 Sep 2015 (actual)
- Study completion
- 13 Sep 2015 (actual)
- First posted
- 3 Jun 2014 (estimated)
- Results
- Posted 24 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
This is a multicenter, Phase 1b/2a, multiple ascending-dose, open-label study designed to assess the safety, tolerability, and efficacy of tesevatinib (KD019) in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study planned to include a Phase 2a expansion in which approximately 50 subjects would receive tesevatinib at the maximum tolerated dose (MTD) dose determined in Phase 1b.
The study employs a successive cohort dose-escalation designed to determine the MTD of tesevatinib in combination with trastuzumab. The MTD dose is defined as the dose level below in which : (a) 2 of 3 subjects (or 2 of 6 subjects if Grade ≥ 3 tesevatinib related treatment emergent adverse event [TEAE] experience in 1 of the first 3 subjects).
In the Phase 1b portion of the study, tesevatinib is to be administered orally (PO) to successive cohorts of subjects at 150 mg, 250 mg, 300 mg, 350 mg, and 400 mg once daily (QD).
The following 4 dossing cohorts are initiated during the study:
- Cohort 1: 150 mg tesevatinib PO QD
- Cohort 2: 250 mg tesevatinib PO QD
- Cohort 3: 300 mg tesevatinib PO QD
- Cohort 4: 350 mg tesevatinib PO QD
[Note: the sponsor suspended the study before a cohort of subjects were enrolled at tesevatinib 400 mg PO QD.]
Trastuzumab is administered intravenously (IV) at 8 mg/kg as an initial loading dose on Day 1 of Cycle 1, followed by 6 mg/kg IV every 3 weeks thereafter, beginning Day 1 of Cycle 2. Subjects entering the study already on trastuzumab are not to receive the initial loading dose and instead receive trastuzumab 6 mg/kg IV. The first doses of trastuzumab and tesevatinib are administered in the clinic on Study Day 1. Subsequent doses of tesevatinib are to be taken on an outpatient basis for the remainder of each 21-day cycle. During Cycle 1, subjects are to be returned to the clinic for weekly safety and tolerability assessments.
Tumor response, both in the central nervous system (CNS) and peripheral to the CNS, is to be assessed after the second cycle of treatment and then at the end of every 2 cycles of treatment thereafter. Subjects are to be treated until disease progression or the subject experienced unacceptable toxicity. Subjects who demonstrated tumor progression are to stop study drug and followed for survival. All subjects discontinuing tesevatinib therapy are to be followed for survival.
Safety assessments include adverse event monitoring, electrocardiograms (ECGs), laboratory testing, physical examinations, vital signs, and pregnancy testing.
An End-of-Treatment visit is to be conducted as soon as possible after the subject's last dose of study drug. This could occur at the visit when disease progression is diagnosed. Subjects are to be followed for disease progression and survival.
A follow-up visit planned for 30 days (± 5 days) after the last dose of study drug assessments is to include collection of AE (Adverse Event) and concomitant medication data. This visit could occur prior to 30 days if a new therapy is started within 30 days of last dose of study drug.
For long-term follow-up, subjects are to be contacted by telephone every 8 weeks to assess survival status and any subsequent anti-cancer treatment.
The duration of treatment for subjects with tesevatinib in combination with trastuzumab is planned until the subject experiences disease progression or unacceptable toxicity.
[Note: Changes to the Planned Analysis: The study, planned to include a Phase 2a expansion in which approximately 50 subjects would have received tesevatinib at the MTD dose determined in Phase 1b, was terminated early. Although some patients had prolonged stable disease in the study, no clear treatment responses were observed. The sponsor decided to suspend the study while gathering additional data from other tesevatinib oncology studies. The study was subsequently terminated early because the sponsor stopped evaluations of tesevatinib as a treatment for HER2-positive metastatic breast cancer.]
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- A phase 1b ascending dose-finding study for establishing the maximum tolerated dose (MTD) of tesevatinib (with trastuzumab).
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Drug: Tesevatinib, Drug: TrastuzumabTesevatinib in combination with Trastuzumab: tesevatinib 150 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. |
| Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Drug: Tesevatinib, Drug: TrastuzumabTesevatinib in combination with Trastuzumab: tesevatinib 250 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. |
| Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Drug: Tesevatinib, Drug: TrastuzumabTesevatinib in combination with Trastuzumab: tesevatinib 300 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. |
| Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV | Experimental | Drug: Tesevatinib, Drug: TrastuzumabTesevatinib in combination with Trastuzumab: tesevatinib 350 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Female ≥ 18 years old.
- 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 (FISH) or silver in situ hybridization (SISH) 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 of the study and in Group 1 and Group 3 of the Phase 2a portion of the study may have received any number of prior therapies for breast cancer. Subjects in Group 2 of the Phase 2a portion of the study may have received up to 3 lines of therapy in the metastatic setting (not including adjuvant or neoadjuvant therapy).
- Subjects with disease progression in the brain after prior brain radiation therapy may have extra-CNS metastases in any location or may have no extra-CNS metastases.
Key exclusion criteria (12 listed)
- Any concurrent therapy for breast cancer other than the specified treatment in this study. Concurrent treatment with bisphosphonates or denosumab is allowed, if started prior to the start of tesevatinib administration.
- Cerebrospinal fluid (CSF) cytology positive for malignant cells or symptomatic leptomeningeal carcinomatosis in the Phase 1b portion of the study. Note: In Group 3 of the Phase 2a portion of the study, 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, including anti-arrhythmic medications within 2 weeks prior to Day 1 of treatment in the study. A stable regimen (≥ 4 weeks) of antidepressants of the SSRI(selective serotonin reuptake inhibitor) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine).
- Has evidence of active heart disease such as myocardial infarction within the 3 months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction.
- History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR(partial response) interval only), or congenital long QT syndrome. Subjects with a history of atrial arrhythmias should be discussed with the medical monitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TesevatinibAlso: KD019, XL647 | Drug | Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV, Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV, Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV, Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV |
| Trastuzumab | Drug | Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV, Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV, Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV, Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV |
Primary outcome
Safety and Tolerability: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) by Severity and/or Relationship to Tesevatinib
Time frame: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up
Percentage of subjects with at least 1 treatment-emergent adverse event of Grade 3 or greater or relationship with tesevatinib. TEAE grading was by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) where Grade 3 is severe and Grade 4 is life-threatening. TEAEs were considered related to study drug if the investigator assessed them as possibly related, probably related, or related.
Safety and Tolerability: Percentage of Subjects With Serious Adverse Event (SAE) Related to Tesevatinib
Time frame: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up
Percentage of subjects with at least 1 serious adverse event considered related to study drug. SAEs were considered related to tesevatinib drug if the investigator assessed them as possibly related, probably related, or related.
5 secondary outcomes
Pharmacokinetics (PK): Mean Serum Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
Time frame: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Median Serum Tmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
Time frame: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Mean Serum AUC(0-t) (Area Under Curve) of Treatment With Tesevatinib + Trastuzumab
Time frame: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Mean AR Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
Time frame: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics: Mean AR AUC(0-24hr) After 1 Cycle of Treatment With Tesevatinib + Trastuzumab
Time frame: PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tesevatinib and Trastuzumab in people with HER-2 Positive Breast Cancer and Metastatic Malignant Neoplasm to Brain, run by Kadmon Corporation, LLC at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) by Severity and/or Relationship to Tesevatinib (time frame: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.