EUCTR2013-002872-42-IE进行中（未招募）1 期
An open-label, Phase 2 basket study of neratinib in patients with solid tumors with somatic activating HER mutations
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 650
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Men and women who are =18 years old at signing of informed consent.
- •2. At time of screening, histologically confirmed cancers in patients with previously documented activating EGFR (exon 18) or qualifying HER2 mutation and who are refractory to standard therapy or for which standard or curative therapy does not exist or is not considered sufficient or appropriate
- •3. At least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1; Eisenhauer et al, 2009).
- •4. Left ventricular ejection fraction (LVEF) =50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
- •5. Eastern Cooperative Oncology Group (ECOG) status of 0 to 2.
- •6. Female patients with cancers known to secrete ß-human chorionic gonadotropin (hCG), ie germinomas, are eligible if the pattern of serum ß-hCG is suggestive of the malignancy and the pelvic ultrasound is negative for pregnancy.
- •7. Male patients must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of trastuzumab, fulvestrant, or neratinib monotherapy. Patients of childbearing
- •potential must agree and commit to the use of a highly effective double-barrier method of contraception or a non-hormonal method, from the signing of the informed consent until:
- •i. 28 days after the last dose of neratinib monotherapy, or
- •ii. 7 months after last dose of trastuzumab or
- •iii. 1 year after the last dose of fulvestrant.
- •8. Written, informed consent to participate in the study and follow the study procedures.
- •9. Recent metastatic tumor sample or fresh tumor biopsy, and plasma/blood specimens for gene sequencing and other biomarker analysis.
- •Additional Inclusion Criteria for all Breast Cancer Patients with Tumors that Harbor HER2 Mutations and NSCLC patients that harbor EGFR exon 18 mutations
- •10. Pretreatment fresh biopsy within 28 days prior to starting treatment unless the biopsy procedure presents a safety concern.
- •Additional Inclusion Criteria for HR+ Breast Cancer Patients with Tumors that Harbor HER2 Mutations
- •11. HR+ disease defined as =1% estrogen receptor (ER) positive and/or progesterone receptor (PR) positive cells:
- •12. Biopsy from a non-bony metastatic site.
- •13. Postmenopausal.
- •14. Medically confirmed ovarian failure
- •15. Pre/perimenopausal if amenable to be treated with a luteinizing hormone receptor hormone (LHRH) agonist.
- •16. Prior treatment with chemotherapy or hormonal therapy (including fulvestrant).
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 325
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 325
排除标准
- •1. Patients harboring ineligible somatic HER2 mutations.
- •2. Prior treatment with pan HER, HER2 or EGFR-directed tyrosine kinase inhibitor (TKI) (eg, lapatinib, afatinib, dacomitinib, neratinib, tucatinib, gefitinib, erlotinib, osimertinib) is excluded with the following exception:
- •patients with EGFR exon 18 mutated non-small cell lung cancer (NSCLC) who may have received afatinib, osimertinib, or other pan-HER or EGFR TKIs remain eligible.
- •3. Not recovered to at least Grade 1 at screening (Common Terminology Criteria for Adverse Events v4.0 [CTCAE v4.0]) from all clinically significant adverse events related to prior therapies (excluding alopecia).
- •4. Received chemotherapy or biologic therapy =2 weeks or 5 half-lives (t½) of the agent used, whichever is shorter, prior to the initiation of investigational product.
- •5. Received radiation therapy =14 days prior to initiation of investigational product.
- •6. Patients who are receiving any other anticancer agents with the exception of patients on 1) a stable dose of bisphosphonates or denosumab or 2) sex hormone therapy in the case of breast, or gynecological cancers.
- •7. Received prior therapy resulting in a cumulative epirubicin dose >900 mg/m2 or cumulative doxorubicin dose >450 mg/m2. If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 450 mg/m2 doxorubicin.
- •8. Symptomatic or unstable brain metastases.
- •9. Active uncontrolled cardiac disease, including cardiomyopathy,congestive heart failure (New York Heart Association functional classification of =2), unstable angina (symptomatic angina pectoris within the past 180 days that required the initiation of or increase in anti-anginal medication or other intervention), myocardial infarction within 12 months of enrollment, or ventricular arrhythmia (except for benign premature ventricular contractions).
- •10. Demonstrates a QTc interval >450 ms for men or >470 ms for women or known history of congenital QT prolongation or Torsade de pointes (TdP).
- •11. Inadequate bone marrow, renal or hepatic function as defined on screening laboratory assessments outside the following limits:
- •Laboratory endpoint: Required limit for exclusion
- •Absolute neutrophil count (ANC): <1,000/µL (1.0 x 109 /L)
- •Platelet count: <100,000/µL (<100 x 109/L)
- •Hemoglobin: <8 g/dL (transfusion allowed to treat low hemoglobin)
- •Transfusion must be at least 7 days prior to C1D1.
- •Total bilirubin: >1.5 x institutional upper limit of normal (ULN) (in case of known Gilbert’s syndrome, >2x ULN)
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT): >3 x institutional ULN
- •OR >5 x ULN if liver metastases are present
- •Creatinine: >1.5 x institutional ULN OR Calculated Creatinine Clearance <30 mL/min (as measured directly with a 24-hour urine or calculated by Cockcroft-Gault or Modification of Diet in Renal Disease [MDRD])
- •12. Active infection or unexplained fever >38.5°C (101.3°F).
- •13. Women who are pregnant, are planning on becoming pregnant, or are breast-feeding.
- •14. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn’s disease, malabsorption, or Grade =2 [CTCAE version 4.0] diarrhea of any etiology at baseline).
- •15. Clinically active infection with a hepatitis virus.
- •16. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investiga
研究者
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