Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer

Completed · Phase 2

Conditions studied: HER2-mutant Non-Small Cell Lung Cancer

In brief

This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations.

Key facts

Study ID

NCT01827267

Run by

Puma Biotechnology, Inc.

People needed

62

Starts

2013-07-01

Expected to finish

2017-10-06

Last updated by the study team

2018-07-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Aged ≥18 years at the time of signing the informed consent.
• Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage IV).
• Documented somatic ErbB2 (HER2) activating mutation.
• Patients with anaplastic lymphoma kinase (ALK) translocations must have received crizotinib, except for cases of intolerable toxicity to crizotinib.
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) status <2.
• Left ventricular ejection fraction (LVEF) ≥50% measured by multiple -gated acquisition scan (MUGA) or echocardiogram (ECHO).
• Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause.
• Men and women of childbearing potential must agree and commit to the use of a highly effective method of contraception, as determined to be acceptable by the Investigator, from the time of informed consent until 3 months after the last dose of the investigational products.
• Provide written, informed consent to participate in the study and follow the study procedures.

You may not qualify if…

• Previous treatment with any investigational agent ≤14 days prior to the initiation of investigational products.
• Previous treatment with any strong inhibitor and/or inducer of CYP3A4 enzyme or sensitive P-glycoprotein (P-gp) substrates ≤30 days prior to the initiation of investigational products.
• Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
• Major surgery <30 days of starting treatment.
• Chronic steroid use (prednisone >12.5 mg/day or dexamethasone >2 mg/day, excluding inhaled steroids).
• Currently breast feeding.
• Symptomatic or unstable brain metastases.
• QTc interval >0.450 seconds for men and >0.470 seconds for women, or known history of QTc prolongation or Torsades de Pointes (TdP).
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any etiology at baseline).
• Prior exposure to neratinib or mTOR inhibitor.
• Active infection or unexplained fever >38.5°C (101.3°F).
• Unable or unwilling to swallow tablets.
• Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
• Known hypersensitivity to any component of the investigational products.
• Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin [HbA1c] >6.5%).
• Screening laboratory assessments outside the following limits: ANC <1000/μL (<1.0 x 109/L), Platelet count <75,000/μL (<75 x 109/L), Hemoglobin <8 g/dL, transfusions allowed, must be at least 7 days prior to baseline, Total bilirubin >1.5 x institutional upper limit of normal (ULN), AST and/or ALT 5 minutes, Creatinine clearance <50 mL/min.

Where it is running

• City of Hope — Duarte, California, United States
• University of California Los Angeles — Santa Monica, California, United States
• University of Colorado — Aurora, Colorado, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Johns Hopkins — Baltimore, Maryland, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Massachusettes General Hospital — Boston, Massachusetts, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Memorial Sloan-Kettering Cancer Center — New York, New York, United States
• Ohio State University — Columbus, Ohio, United States
• University of Pittsburgh Cancer Institute — Pittsburgh, Pennsylvania, United States
• Vanderbilt University — Nashville, Tennessee, United States
• UT Southwestern Medical Center — Dallas, Texas, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• CHU de Grenoble Hopital Albert Michallon — Grenoble, France
• CHRU de Lille - Hopital Calmette — Lille, France
• Hopital Nord — Marseille, France
• Hopitaux universitaires de Strasbourg Nouvel Hopital Civil — Strasbourg, France
• CHU de Toulous Hopital Larre — Toulouse, France
• Institut Gustave Roussy — Villejuif, France

Full record on ClinicalTrials.gov

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