Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers

Lung Cancer Clinical Trial

Official title:

A Phase 2 Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02675829
• Other study ID #: 15-335
• Status: Recruiting
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: February 2025

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Bob Li, MD
• Phone: 646-608-3791
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out what effects, a drug called ado-trastuzumab emtansine has on the patient and their cancer which is thought to be controlled by the abnormal HER2 gene.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults who are =18 years old.

• Pathologically confirmed advanced solid tumor cancers

• For Cohort 1, documented activating HER2 mutation in lung cancer by CLIA laboratory, specifically exon 20 insYVMA (Y772_A775dup), insGSP (G778_P780dup), insTGT (G776delinsVC), single base pair substitutions L755A, L755S, V777L, V659E, S310F, or another HER2 mutation approved by the Principal Investigator

• For Cohorts 2, 3, 4, 5, 6 documented HER2 amplification identified through next generation sequencing by MSK-IMPACT or at another Clinical Laboratory Improvement Amendments (CLIA) laboratory, or documented HER2 amplification by in-situ hybridization (ISH) with HER2/CEP17 ratio =2.0 at a CLIA laboratory. Patients with HER2 amplification identified by another method or criteria must be approved by the Principal Investigator and may enroll in the "Other" Cohort 4.

• Measurable or evaluable indicator lesion(s) as defined by RECIST v1.1. Patients without RECIST measurable disease will be eligible for enrollment to "Other" cohort provided their disease can be evaluated using another accepted response criteria (e.g. Gynecologic Cancer InterGroup (GCIG) CA125 Response Criteria, modified PET Response Criteria in Solid Tumors (PERCIST)). Patients with salivary gland cancers (Cohort 5) may be eligible on the basis of evaluable disease on modified PET.

• Karnofsky Performance Status 70% or above.

• Left ventricular ejection fraction (LVEF) =50% measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA).

• Negative ß-human chorionic gonadotropin (hCG) pregnancy test within 2 weeks before enrollment for premenopausal women of reproductive capacity and for women less than 12 months after menopause. Pregnancy screening will be conducted for women up to the age of 50 years per institutional standard.

• Women of childbearing potential must agree to use of a highly effective method of contraception. Effective contraception is required during treatment and for 7 months following the last dose for female participants of reproductive potential and during treatment and for 4 months following the last dose for male participants with female sexual partners of reproductive potential. Male participants should also refrain from donating sperm during treatment and for 4 months following the last dose.

• Absolute neutrophil count = 1,000/µL within 30 days prior to C1D1

• Platelet count = 100,000/µL within 30 days prior to C1D1

• Total bilirubin = 1.5 x institutional upper limit of normal (ULN), in case of Gilbert's syndrome, = 2x ULN within 30 days prior to C1D1

• Aspartate aminotransferase and/or alanine aminotransferase = 3 x ULN (= 5 x ULN if liver metastases are present) within 30 days prior to C1D1

• Provide written, informed consent to participate in the study and follow the study procedures

Exclusion Criteria:

• Prior therapy resulting in cumulative epirubicin dose = 900mg/m2 or cumulative doxorubicin dose = 500mg/m2 or equivalent dose of another anthracycline.

• Prior therapy with ado-trastuzumab emtansine (patients who had prior trastuzumab or other HER2 targeted agents are eligible).

• Symptomatic congestive heart failure (New York Heart Association Classification II-IV).

• Myocardial infarction or unstable angina within 6 months of enrollment.

• Unstable ventricular arrhythmia requiring treatment.

• Grade 3 or worse peripheral neuropathy as defined by CTCAE v4.1.

• Women who are pregnant or breast-feeding.

• Known hypersensitivity to any component of ado-trastuzumab emtansine.

• History of interstitial lung disease or pneumonitis.

Related Conditions & MeSH terms

• Bladder Cancer
• Lung Cancer
• Solid Tumor Cancers
• Urinary Tract Cancers
• Urologic Neoplasms

Intervention

Drug:
• ado-trastuzumab emtansine
Ado-trastuzumab emtansine is administered intravenously at 3.6 mg/kg every 21 days (unless dose reduction and/or dose delays are required) until disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	best overall response (ORR)	As soon as evaluations for each tumor assessment are completed, the Investigator should assess the patient's overall response (target plus non- target lesions) based on criteria and overall response algorithms as defined in RECIST version 1.1. Scans must be assessable for all evaluations.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center