A study of Neratinib in patients with solid tumours that have specific genetic mutations
- Conditions
- Malignant solid tumor with somatic human epidermal growth factor receptor (EGFR, ERBB2, ERBB3) mutations or EGFR amplification (primary brain tumors).MedDRA version: 20.0Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 100000020935Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-002872-42-FI
- Lead Sponsor
- Puma Biotechnology, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 292
1. Men and women who are =18 years old at signing of informed consent.
2. Histologically confirmed cancers in patients with activating ERBB mutations and/or EGFR amplification and who are refractory to standard therapy or for which standard or curative therapy does not exist or is not considered sufficient or appropriate by the Investigator.
3. At the time of screening, a previously documented mutation:
i. ERBB2 mutation in breast, bladder/urinary tract, biliary tract, colorectal, endometrial, gastroesophageal, lung, ovarian, and any other cancers, or
ii. EGFR mutation/amplification in a primary brain tumor, or
iii. ERBB3 mutation in any cancer.
4. At least one measurable lesion, preferably as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1; Eisenhauer et al, 2009). Patients without RECIST measurable disease may be eligible for enrollment provided their disease can be evaluated for response using another accepted criteria (eg, Gynecologic Cancer InterGroup [GCIG] CA125 Response Criteria [Rustin et al, 2011], Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Criteria [Scher et al, 2008]; PET Response Criteria [PET Response Criteria]).
5. Left ventricular ejection fraction (LVEF) =50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
6. Eastern Cooperative Oncology Group (ECOG) status of 0-2.
7. 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.
8. Men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of the IP. Women of child-bearing potential must agree and commit to the use of a highly effective double-barrier method of contraception (eg, a combination of male condom with an intravaginal device such as the cervical cap, diaphragm, or vaginal sponge with spermicide) 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. 6 months after the last dose of paclitaxel, or
iii. 1 year after the last dose of fulvestrant.
9. Provide written, informed consent to participate in the study and follow the study procedures.
10. A biomarker request form for the patient’s mutation has been signed and approved for eligibility by the Sponsor.
Details for additional Inclusion Criteria for Patients with Primary Breast Tumors that Harbor ERBB2 Mutations AND for Patients with Primary Brain Tumors that Harbor EGFR Mutations (closed to enrollment in Amendment 4) can be found in the protocol.
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 146
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 146
1. Prior treatment with any ERBB2-directed TKI (eg, lapatinib, afatinib, dacomitinib, neratinib) with the exception of NSCLC patients who may have received afatinib and remain eligible.
2. Not recovered to at least Grade 1 or baseline (CTCAE V4.0) from all clinically significant AEs related to prior therapies (excluding alopecia).
3. Received chemotherapy or biologic therapy =2 weeks or 5 half-lives (t½) of the agent used, whichever is shorter, prior to the start of neratinib.
4. Received radiation therapy =14 days prior to initiation of IP, except primary brain tumor patients.
5. 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, prostate or gynecological cancers.
6. 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.
7. Symptomatic or unstable brain metastases. Patients with primary central nervous system tumors are eligible.
8. 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). For patients with NSCLC, the following are additionally excluded: conduction abnormality requiring a pacemaker; supraventricular and/or nodal arrhythmias not controlled with medication; valvular disease with documented compromise in cardiac function; symptomatic pericarditis; any history of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; any history of documented congestive heart failure and/or cardiomyopathy.
9. 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).
10. Inadequate bone marrow, renal or hepatic function as defined on screening laboratory assessments outside the following limits:
- Absolute neutrophil count (ANC): <1,000/µL (1.0 x 10e9 /L);
- Platelet count <100,000/µL (<100 x 10e9/L);
- Hemoglobin: <8 g/dL (transfusion allowed to treat low haemoglobin) Transfusion must be at least 7 days prior to baseline;
- Total bilirubin: >1.5 x institutional ULN (in case of known Gilbert's syndrome, >2× ULN);
- Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT): >3 x institutional ULN OR >5 × ULN if liver metastases are present;
- Creatinine: >1.5 × institutional ULN or calculated Creatinine Clearance <30 mL/min (as calculated by Cockroft-Gault formula or MDRD formula).
11. Uncontrolled concurrent malignancy (early stage or chronic disease is allowed if not requiring active therapy or intervention and is under control).
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 National Cancer
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method