Tucatinib, Trastuzumab, and Capecitabine for the Treatment of HER2+ LMD
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03501979|
Recruitment Status : Recruiting
First Posted : April 18, 2018
Last Update Posted : April 12, 2021
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer Leptomeningeal Disease||Drug: Tucatinib Drug: Trastuzumab Drug: Capecitabine||Phase 2|
The purpose of this study is to evaluate a new treatment for patients with HER2+ metastatic breast cancer (MBC) with leptomeningeal disease (LMD). This is a rare and fast-growing form of cancer. Leptomeningeal disease refers to the seeding of tumor cells to the leptomeninges and dissemination in the cerebrospinal fluid.
Currently, there are is no standard of care treatment for LMD. However, we think the combination therapy will be safe and well-tolerated and may also improve survival. Blood and spinal fluid samples will be collected to evaluate the effects on the body and the cancer, which will help provide greater understanding to therapy response in patients.
The study has a two-stage design with the first stage including 15 subjects from up to ten institutions nationwide. If it advances to the second stage based on the number of successes, another 15 subjects will be enrolled.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Subjects will receive combination treatment with tucatinib + trastuzumab + capecitabine every 21 days, which is one cycle. Evaluation will be done every two cycles with an MRI of the brain and spine. Cycles 3 and beyond will be at the discretion of the physician. A scan will be done every four cycles.|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Non-randomized Study to Assess the Safety and Efficacy of the Combination of Tucatinib and Trastuzumab and Capecitabine for Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer|
|Actual Study Start Date :||March 6, 2019|
|Estimated Primary Completion Date :||September 2022|
|Estimated Study Completion Date :||September 2023|
Experimental: 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 study drug is given in tablet form and taken daily.
Other Name: ONT-380
Trastuzumab is approved by the FDA and is available commercially. Trastuzumab must be prepared and is administered intravenously.
Capecitabine is approved by the FDA and is available commercially as an oral drug.
- Overall survival [ Time Frame: From date of study enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 3 years ]Length of subject survival after starting study treatment. A Gehan-like trial design with an interim futility analysis will be used.
- Number of adverse events [ Time Frame: Baseline up to 3 years or until disease progression or unacceptable toxicity or death. ]Adverse 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.
- Progression free survival [ Time Frame: Baseline to 12 weeks ]From the start of treatment to 12 weeks
- Objective response in the central nervous system (CNS) [ Time Frame: Baseline up to 3 years ]Data 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.
- Clinical benefit rate (CBR) in CNS [ Time Frame: Baseline to 3 years ]The 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.
- Objective response in extra-CNS disease [ Time Frame: Baseline up to 3 years ]Data 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.
- Clinical benefit rate (CBR) in extra-CNS disease [ Time Frame: Baseline to 3 years ]The 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.
- Symptom Burden [ Time Frame: Beginning at baseline and every 21 days until the end of study up to three years ]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.
- Quality of Life Assessment [ Time Frame: Beginning at baseline and every 42 days until the end of study up to three years ]The Linear Analog Scale Assessment Quality of Life will be used to evaluate changes in the quality of life at restaging visits.
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): NCT03501979
|Contact: Erica M Stringer-Reasor, MDfirstname.lastname@example.org|
|Contact: Pam Dixon Hardwick, RN, BSN, OCNemail@example.com|
|United States, Alabama|
|University of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Contact: Erica M Stringer-Reasor, MD 205-975-2816 firstname.lastname@example.org|
|United States, California|
|San Francisco, California, United States, 94158|
|Contact: Michelle Melisko, MD|
|United States, District of Columbia|
|MedStar Georgetown University-Lombardi CCC||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Paula Pohlmann, MD|
|United States, Illinois|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637-1470|
|Contact: Rita Nanda, MD|
|United States, Indiana|
|Indiana University-Melvin and Bren Simon cancer center||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Kathryn Nevel, MD|
|United States, Massachusetts|
|Dana Farber/Harvard Cancer Center-||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Jose Leone, MD|
|United States, Michigan|
|University of Michigan-||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Aki Morikawa, MD|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Rashmi K Murthy, MD, MBE email@example.com|
|United States, Washington|
|University of Washington Medical Center-Montlake||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Jennifer Specht, MD|
|Principal Investigator:||Erica M Stringer-Reasor, MD||University of Alabama at Birmingham|
|Study Chair:||Rashmi K Murthy, MD, MBE||M.D. Anderson Cancer Center|
|Study Chair:||Barbara J O'Brien, MD||M.D. Anderson Cancer Center|