Trial Outcomes & Findings for Tucatinib, Trastuzumab, and Capecitabine for the Treatment of HER2+ LMD (NCT NCT03501979)
NCT ID: NCT03501979
Last Updated: 2025-08-29
Results Overview
Number of participants alive. A Gehan-like trial design with an interim futility analysis will be used.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Through study completions, an average of 2 years
Results posted on
2025-08-29
Participant Flow
Participant milestones
| Measure |
Tucatinib + Trastuzumab + Capecitabine
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
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|---|---|
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Overall Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
17
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Tucatinib, Trastuzumab, and Capecitabine for the Treatment of HER2+ LMD
Baseline characteristics by cohort
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
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Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
53 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
|
17 participants
n=5 Participants
|
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Patient Demographics
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Through study completions, an average of 2 yearsNumber of participants alive. A Gehan-like trial design with an interim futility analysis will be used.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
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|---|---|
|
Length of Subject Survival After Starting Study Treatment
|
6 Participants
|
SECONDARY outcome
Timeframe: up to 28 monthsAdverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Subjects who receive at least one dose of the drug combination will be evaluable for toxicity from the time of the first dose.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
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|---|---|
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Number of Adverse Events
diarrhea
|
13 participants
|
|
Number of Adverse Events
fatigue
|
9 participants
|
|
Number of Adverse Events
nausea/vomiting
|
8 participants
|
|
Number of Adverse Events
hand-foot syndrome
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13 participants
|
|
Number of Adverse Events
liver function test elevation
|
11 participants
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SECONDARY outcome
Timeframe: up to 12 monthsFrom the start of treatment to 12 months
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
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|---|---|
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Progression Free Survival
|
10 months
Interval 4.1 to 10.0
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SECONDARY outcome
Timeframe: up to 28 monthsData from subjects who have received at least one cycle of therapy and disease re-evaluation for CNS tumors by imaging, cytopathology, and clinical evaluation will be accumulated until disease progression.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Duration of Response in the Central Nervous System (CNS)
|
6.9 months
Interval 2.8 to 13.8
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SECONDARY outcome
Timeframe: Baseline up to 28 monthsThe overall survival from the combination therapy is compared to the historical control. Clinical benefit is observed with a ratio of successes and corresponding confidence interval.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Clinical Benefit Rate (CBR) in CNS
|
6 Participants
|
SECONDARY outcome
Timeframe: up to 28 monthsData from subjects who have received at least one cycle of therapy and disease re-evaluation for extra-CNS tumors by imaging, cytopathology, and clinical evaluation will be accumulated until disease progression. Extra-CNS response will be classified per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Duration of Response in Extra-CNS Disease
|
4.1 months
Interval 2.3 to 11.4
|
SECONDARY outcome
Timeframe: up to 28 monthsThe overall survival from the combination therapy is compared to the historical control. Clinical benefit is observed with a ratio of successes and corresponding confidence interval.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Clinical Benefit Rate (CBR) in Extra-CNS Disease
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline, end of study (up to 28 months)The M.D. Anderson Symptom Inventory Brain Tumor (MDASI -BT) module questionnaire will collect data at each study time point and evaluate changes of symptom burden. The MDASI-BT scale measures the severity of symptoms experienced by patients with breast cancer that interfere with daily living. A greater number of symptoms equals a greater interference with daily living. Symptoms of severity are assessed on a 0-213 scale with 0 being "lower quality of life" and 213 "higher quality of life".
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=12 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
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|---|---|
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Symptom Burden
baseline
|
61 score on a scale
Interval 0.0 to 213.0
|
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Symptom Burden
end of study
|
32 score on a scale
Interval 0.0 to 213.0
|
SECONDARY outcome
Timeframe: up to 28 monthsThe Linear Analog Scale Assessment Quality of Life will be used to evaluate changes in the quality of life at restaging visits. Scale ranges from 0 to 100. Higher scores indicate a better quality of life.
Outcome measures
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 Participants
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Quality of Life Assessment
|
31 score on a scale
Interval 11.0 to 47.0
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Adverse Events
Tucatinib + Trastuzumab + Capecitabine
Serious events: 1 serious events
Other events: 13 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 participants at risk
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Gastrointestinal disorders
Elevated liver function test
|
5.9%
1/17 • Number of events 1 • Patients were monitored for adverse events while on study drugs and up to 1 month after discontinuation of study drug (up to 28 months).
|
Other adverse events
| Measure |
Tucatinib + Trastuzumab + Capecitabine
n=17 participants at risk
Tucatinib will be taken orally at 300 mg twice a day starting with Cycle 1, Day 1. A cycle consists of 21 days. Capecitabine will be taken orally at 1000 mg/m2 twice a day on Days 1-14 starting with cycle 1. Trastuzumab is given intravenously as a loading dose of 8 mg/kg on Cycle 1, Day 1 and then at 6 mg/kg for all subsequent cycles.
Tucatinib: Tucatinib study drug is given in tablet form and taken daily.
Trastuzumab: Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine: Capecitabine is approved by the FDA and is available commercially as an oral drug.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
76.5%
13/17 • Number of events 13 • Patients were monitored for adverse events while on study drugs and up to 1 month after discontinuation of study drug (up to 28 months).
|
|
General disorders
Fatigue
|
58.8%
10/17 • Number of events 10 • Patients were monitored for adverse events while on study drugs and up to 1 month after discontinuation of study drug (up to 28 months).
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
58.8%
10/17 • Number of events 10 • Patients were monitored for adverse events while on study drugs and up to 1 month after discontinuation of study drug (up to 28 months).
|
|
Skin and subcutaneous tissue disorders
Hand Foot Syndrome
|
76.5%
13/17 • Number of events 13 • Patients were monitored for adverse events while on study drugs and up to 1 month after discontinuation of study drug (up to 28 months).
|
|
Gastrointestinal disorders
Elevated liver function test
|
64.7%
11/17 • Number of events 11 • Patients were monitored for adverse events while on study drugs and up to 1 month after discontinuation of study drug (up to 28 months).
|
Additional Information
Dr. Erica Stringer-Reasor
University of Alabama at Birmingham
Phone: 205-975-2914
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place