Status:
COMPLETED
Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer
Lead Sponsor:
Puma Biotechnology, Inc.
Conditions:
HER2-mutant Non-Small Cell Lung Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patien...
Detailed Description
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patien...
Eligibility Criteria
Inclusion
- Inclusion Criteria
- 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.
- Exclusion Criteria
- 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.
Exclusion
Key Trial Info
Start Date :
July 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 6 2017
Estimated Enrollment :
62 Patients enrolled
Trial Details
Trial ID
NCT01827267
Start Date
July 1 2013
End Date
October 6 2017
Last Update
July 3 2018
Active Locations (21)
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1
City of Hope
Duarte, California, United States, 91010
2
University of California Los Angeles
Santa Monica, California, United States, 94040
3
University of Colorado
Aurora, Colorado, United States, 80045
4
Moffitt Cancer Center
Tampa, Florida, United States, 33612