A Study of Tucatinib Given Before Surgery to People With HER2+ Cancers That Have Spread to the Brain

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05892068

Collaborator

Seagen Inc. (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Tucatinib	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The study design includes patient candidates for clinically indicated craniotomy in three parallel cohorts.The study design includes patient candidates for clinically indicated craniotomy in three parallel cohorts.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Window of Opportunity Analysis of Pre-Operative Tucatinib for Surgically Resected HER2+ Brain Metastases: Understanding Mechanisms of Resistance

Actual Study Start Date :

May 9, 2023

Anticipated Primary Completion Date :

May 9, 2028

Anticipated Study Completion Date :

May 9, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients already on Tucatinib Cohort A: This is a non-interventional study patients who will enter while already on Tucatinib . Patients in cohort A who are already on Tucatinib at a dose reduction (i.e., for toxicity) will continue the same dose.	Drug: Tucatinib Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).
Experimental: Patients with documented radiological and/or clinical CNS progression with no prior tucatinib Cohort B: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).	Drug: Tucatinib Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).
Experimental: HER2+ esophagogastric, lung, or colon cancer brain metastases and HER2 mutant breast cancer Cohort C: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).	Drug: Tucatinib Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Arm

Intervention/Treatment

Experimental: Patients already on Tucatinib

Cohort A: This is a non-interventional study patients who will enter while already on Tucatinib . Patients in cohort A who are already on Tucatinib at a dose reduction (i.e., for toxicity) will continue the same dose.

Drug: Tucatinib

Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Experimental: Patients with documented radiological and/or clinical CNS progression with no prior tucatinib

Cohort B: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Drug: Tucatinib

Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Experimental: HER2+ esophagogastric, lung, or colon cancer brain metastases and HER2 mutant breast cancer

Cohort C: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Drug: Tucatinib

Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Outcome Measures

Primary Outcome Measures

Maximum observed plasma concentration (Cmax) of Tucatinib [3 days after treatment]
by measurement of intrametastasis levels

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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:

Absolute neutrophil count (ANC) ≥1.0 × 103μL, Platelet count ≥75 × 103 /μL, Hemoglobin ≥ 8.0 g/dL
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)
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)
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center
Seagen Inc.

Investigators

Principal Investigator: Andrew Seidman, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center

Publications

None provided.

Responsible Party:

Memorial Sloan Kettering Cancer Center

ClinicalTrials.gov Identifier:

NCT05892068

Other Study ID Numbers:

22-168

First Posted:

Jun 7, 2023

Last Update Posted:

Jun 7, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Memorial Sloan Kettering Cancer Center

Additional relevant MeSH terms:

Tucatinib

Study Results

No Results Posted as of Jun 7, 2023