Trial Title:
A Study of Tucatinib Given Before Surgery to People With HER2+ Cancers That Have Spread to the Brain
NCT ID:
NCT05892068
Condition:
Metastatic Breast Cancer
Conditions: Official terms:
Tucatinib
Conditions: Keywords:
Tucatinib
HER2+
Surgery
22-168
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
The study design includes patient candidates for clinically indicated craniotomy in three
parallel cohorts.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tucatinib
Description:
Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).
Arm group label:
HER2+ esophagogastric, lung, or colon cancer brain metastases and HER2 mutant breast cancer
Arm group label:
Patients already on Tucatinib
Arm group label:
Patients with documented radiological and/or clinical CNS progression with no prior tucatinib
Summary:
The purpose of this study to see how the brain absorbs, distributes, and gets rid of
tucatinib in people who have HER2+ cancers (breast cancer, NSCLC, CRC, or GEC) that have
spread to the brain, and to learn more about how cancer cells develop resistance to
treatment. The researchers will do research tests to look for genetic differences between
HER2+ breast cancer that has spread to the brain and progressed during treatment with
tucatinib and cancers that are being treated with tucatinib for the first time.
Detailed description:
All patients will receive tucatinib per-protocol at standard dose of 300 mg orally twice
daily on days - 4, -3, -2, -1 and day 0 (in AM). The post-surgery treatment (systemic
and/or local) will be decided according to treating physician discretion and is not a
study intervention. Tissue samples of brain metastases along with blood/plasma and CSF
samples will be analyzed to evaluate brain tumor penetration of tucatinib as well as
biologic response to tucatinib in patients with brain metastases from HER2+/mutant breast
cancer who are undergoing clinically indicated brain surgery. Patients may continue
tucatinib post-operatively at the discretion of the treating oncologist with monitoring
as per clinical routine; this is not a study intervention for Cohort A and Cohort B.
Patients on Cohort C may receive tucatinib post-operatively through the study according
to physician descretion.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥18 years with no impairment in decision making capacity
- Patients with HER2 overexpressed/amplified/mutant metastatic
breast/lung/esophagogastric/colorectal cancer (IHC, fluorescent in situ hybridation
or sequencing-confirmed primary, brain, or other metastatic site) and one or more
brain tumor(s) planned for neurosurgical resection. Other untreated brain
metastases, and prior radiation (whole brain radiation therapy and/or stereotactic
radiosurgery) to the index site are allowed
- Patients with concomitant leptomeningeal disease are eligible provided they have
parenchymal brain metastases requiring resection.
- Life expectancy of >12 weeks.
- ECOG Performance Status (PS) of 0 to 2
- Prior treatments:
- Cohort A: Clinical and or radiological CNS parenchymal progression on tucatinib
as most recent line of treatment (tucatinib-resistant) in patients with HER2
overexpressed/amplified breast cancer
- Clinical and or radiological CNS parenchymal progression with no prior
tucatinib (tucatinib naïve) in patients with HER2 overexpressed/amplified
breast cancer
- Clinical and or radiological CNS parenchymal progression in patients with
HER2+/mutant lung/esophagogastric/colorectal cancer and HER2 mutant breast
cancer
ALL PATIENTS:
- Prior conventional dose lapatinib and neratinib are allowed in any cohort if > 6
months prior
- No limit on prior lines of systemic therapy
- Adequate bone marrow, liver, renal function, and coagulation parameters (obtained ≤
7 days prior to the first day of study treatment:
1. Absolute neutrophil count (ANC) ≥1.0 × 103μL, Platelet count ≥75 × 103 /μL,
Hemoglobin ≥ 8.0 g/dL
2. Total bilirubin ≤1.5 × upper limit of normal (ULN). Subjects with known history
of Gilbert's Syndrome and normal direct bilirubin, aspartate aminotransferase
(AST), and alanine aminotransferase (ALT) are eligible: AST and ALT ≤2.5 × ULN
(≤5 × ULN if liver metastases are present)
3. Calculated creatinine clearance ≥50 mL/min using the CKD-EPI (2021) (in Cohort
A, in patients with elevated serum creatinine, eGFR can be calculated using
cystatin C to confirm eligibility)
4. International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) ≤1.5 × ULN unless on medication known to alter INR and/or aPTT
- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to enrollment and must agree to use adequate contraception prior
to enrollment and for the duration of study participation
- Patients must be able to swallow and retain oral medication
Exclusion Criteria:
- Contraindications or history of allergic reaction to tucatinib or any of its
excipients
- Significant medical co-morbidities as per investigator evaluation
- Inability to comply with protocol and /or not willing or not available for follow-up
assessments or any condition which in the investigator's opinion makes the patient
unsuitable for the study participation
- Have used a strong or moderate CYP2C8 inhibitor within 5 half-lives of the inhibitor
or have used a strong or moderate CYP2C8 or CYP3A4 inducer within 2 weeks prior to
first dose of study treatment (Appendix E)
- Receiving concomitant CYP3A or P-gp substrates where minimal concentration changes
may lead to serious or life-threatening toxicities
- Concurrent pregnancy
Gender:
Female
Gender based:
Yes
Gender description:
Breast Cancer
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Cancer Center (Limited Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Facility:
Name:
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Contact backup:
Last name:
Nelson Moss, MD
Phone:
212-639-7075
Investigator:
Last name:
Andrew Seidman, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Seidman, MD
Phone:
646-888-5445
Start date:
May 9, 2023
Completion date:
May 9, 2028
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Pfizer
Agency class:
Industry
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05892068
http://www.mskcc.org/mskcc/html/44.cfm
