HER2 positive breast cancer MedDRA version: 14.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: CUDC-101
Product Code: CUDC-101
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: CUDC-101
Current Sponsor code: CUDC-101
Concentration unit: mg milligram(s)
Con
Sponsors
Curis, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female subjects with invasive breast cancer. 2. Tumour must be confined to either the breast or to the breast and ipsilateral axilla, measuring >15mm. 3. HER2-positive defined using FISH/CISH and/or DAKO +++ positivity. 4. Histologically confirmed through either core needle biopsy or an incisional biopsy. Excisional biopsy will not be allowed. 5. Measurable or evaluable disease amenable to repeated biopsies. 6. Age =18 years. 7. ECOG performance status 0 or 1. 8. Life expectancy =3 months. 9. Neither pregnant nor lactating. 10. If of childbearing potential must agree to use adequate birth control for the duration of the study and for 30 days following the last dose of study drug. Negative pregnancy test within 7 days prior to registration. 11. Absolute neutrophil count =1500/µL; platelets =100,000/µL; serum creatinine = ULN; total bilirubin =1.5x ULN; AST/ALT =2.5x ULN; serum magnesium and potassium within normal limits (may use supplements to achieve normal values). 12. Subjects must agree to two biopsies following their diagnostic biopsy – a pre- and a post- therapy biopsy. 13. Able to provide informed consent and to follow protocol requirements. 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Prior or concurrent systemic anticancer therapy. 2. Prior w thdrawal from hormone replacement therapy = 3 months previously. 3. Prior or concurrent ipsilateral radiation therapy for invasive or non-invasive breast cancer. 4. Evidence of distant metastatic disease (beyond adjacent nodes). 5. Inflammatory breast cancer. 6. Use of investigational agent(s) within 14 days prior to the first dose of study drug. 7. History of cardiac disease with a New York Heart Association Class II or greater congestive heart failure, myocardial infarction or unstable angina in the past 6 months prior to Day 1 of treatment, or serious arrhythmias requiring medication for treatment. 8. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C. 9. Subjects with prolonged QTc interval >450 seconds. 10. Known history of GI bleeding, ulceration, or perforation. 11. Subjects receiving regular warfarin. 12. Known history of stroke or cerebrovascular accident within the past 6 months. 13. Any uncontrolled condition which in the opinion of the Investigator could affect the subject’s participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore changes in tumour levels of Ki-67 and AcH3 measured by IHC from matched biopsies taken pre- and post- short-term 5-day treatment with CUDC-101 given as a 1 hour I.V. infusion at 275 mg/m2 in subjects with HER2 positive invasive breast cancer.;Secondary Objective: 1. To assess the pharmacokinetics of CUDC-101. 2. To assess the safety of short-term treatment with CUDC-101. 3. To measure clinical response to short-term treatment with CUDC-101. 4. To assess additional markers of CUDC-101 pharmacodynamic activity in tumour tissue and peripheral blood mononuclear cells (PBMCs).;Primary end point(s): Changes in levels of Ki-67 and AcH3 as determined by immunohistochemical analysis in paired pre- and post-treatment tumour biopsy specimens, indicative of CUDC-101 pharmacodynamic activity.;Timepoint(s) of evaluation of this end point: Screening visit (Day -14 to Day 1) and Day 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. PK: 0-23 hours post dose 2. AEs throughout study 3. Size of lesions: at screening visit and end of study visit. 4. Other biomarkers: Cohort 1: at screening visit and Day 5; Cohort 2: at screening visit and Day 1;Secondary end point(s): 1. PK endpoints including clearance (Cl), apparent volume of distribution at steady state (Vdss), maximum concentration (Cmax), time of maximum concentration (Tmax), half-life (t1/2), area under the curve (AUC0-inf and AUC0-t), and other relevant parameters. Analysis of the PK parameters will include descriptive statistics such as means, standard deviations, median, maxima, and minima. 2. Incidence of adverse events (CTCAE v.4) and changes from baseline in vital signs, clinical laboratory, and electrocardiography (ECG) parameters. 3. Change in size of lesions measurable by physical examination (i.e., superficial and =10mm diameter as assessed using callipers). 4. Changes in other biomarkers in indicative of CUDC-101 pharmacodynamic activity, such as IHC levels of pHER2, total HER2, pEGFR and EGFR in tumour tissue and AcH3 in PBMCs. | — |
Countries
United Kingdom
Contacts
Public ContactRobert Laliberte
Curis, Inc.
Outcome results
None listed