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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02675829

Collaborator

Genentech, Inc. (Industry)

135

Enrollment

Locations

Arms

Anticipated Duration (Months)

19.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Cancers Lung Cancer Bladder Cancer Urinary Tract Cancers	Drug: ado-trastuzumab emtansine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

135 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2016

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Lung cancers, HER2 mutant	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.
Experimental: Cohort 2: Lung cancers, HER2 amplified	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.
Experimental: Cohort 3: Colorectal cancers	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.
Experimental: Cohort 4: Endometrial cancers	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.
Experimental: Cohort 5: Salivary gland cancers	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.
Experimental: Cohort 6: Other solid cancers	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.

Outcome Measures

Primary Outcome Measures

best overall response (ORR) [2 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 β-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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York	United States	11553