Breast Cancer MedDRA version: 18.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: PM060184
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Not Aplicable
CAS Number: 960210-99-5
Current Sponsor code: PM060184
Other descriptive
Sponsors
Pharma Mar, S.A. , Sociedad Unipersonal
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Voluntarily written informed consent (IC), obtained from the patient before the beginning of any specific study procedures. 2) Age = 18 years. 3) Histologically proven diagnosis of breast cancer. 4) Tumors must be hormone receptor (ER and/or PgR) positive and HER2 negative. 5) Two or three chemotherapy lines in the advanced setting (adjuvant and/or neoadjuvant chemotherapy are allowed). 6) Previous treatment with anthracyclines and taxanes (unless clinically contraindicated for any of them). 7) Disease progression should have occurred within 2 months before study entry and within 6 months of the last administration of chemotherapy for advanced disease. 8) Measurable disease as defined by the RECIST criteria v.1.1. If the only tumor lesion is situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, progression of the lesion must be demonstrated. 9) Patients with dermic metastatic pattern only: lesions should have at least 10 mm diameter assessed by calipers and should be documented by color photography including a ruler to estimate the size of the lesion. 10) Patients with bone metastases will be eligible if other sites of measurable disease are present. 11) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. 12) For patients in both arms, adequate bone marrow, liver and kidney function: a) Hemoglobin = 9 g/dl. b) Neutrophil count = 1.5 × 109/l. c) Platelet count = 100 × 109/l. d) Serum creatinine = 1.5 mg/dl or calculated creatinine clearance = 40 ml/min. e) Albumin = 2.5 g/dl. f) Total serum bilirubin = 1.5 x upper limit of normal (ULN), except in case of Gilbert´s syndrome. g) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 × ULN (= 5.0 x ULN in the presence of liver metastases). 13) Peripheral neuropathy grade = 1 according to the National Cancer Institute Common Terminology Criteria for the Classification of Adverse Events (NCI-CTCAE) (v.4). 14) Complete recovery to grade = 1 from any toxicity due to a previous therapy (except for alopecia) according to the NCI-CTCAE (v.4) criteria. 15) Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards). 16) At least three weeks since the last administration of chemotherapy, biological therapy or investigational drug; six weeks since the last administration of nitrosoureas and mitomycin C, and one week since the last dose of hormone-therapy. 17) At least three weeks since the end of radiotherapy involving up to 35% of the bone marrow (radiotherapy involving > 35% of bone marrow is not allowed) or two weeks since the end of palliative radiotherapy, including single doses. 18) Life expectancy = 3 months. 19) Women of child-bearing potential must have a negative pregnancy test seven days prior to treatment administration; a medically approved method of contraception must be maintained while on treatment with any of the trial medications and for six months after their last administration. Peri-menopausal women must have had amenorrhea for at least 12 months to be considered of non-childbearing potential. 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 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1) Prior exposure to PM060184. 2) Concomitant administration of any other antineoplastic therapy. 3) History of another neoplastic disease (except for prior breast cancer, basal cell carcinoma of the skin, properly treated in situ carcinoma of the uterine cervix, or melanoma in situ), unless in remission for five years or longer and without local or systemic recurrence. 4) Presence of cerebral and/or leptomeningeal metastasis, even if they are being treated. 5) Patients with locally advanced disease amenable to local therapy at study entry. 6) Unknown HR status (both ER and PgR) and HER2 new status. 7) Inflammatory breast carcinoma. 8) Other serious and/or relevant diseases or clinical situations that, in the Investigator´s opinion, are incompatible with the protocol (any of the following): a) History of cardiac disease, such as myocardial infarction, in the year prior to enrollment in the clinical trial; symptomatic/uncontrolled angina pectoris; congestive heart failure or uncontrolled cardiac ischemia; any type of uncontrolled arrhythmia or abnormal left ventricular ejection fraction, or uncontrolled arterial hypertension (according to the standards of the World Health Organization, WHO). b) History of significant psychiatric disease. c) Active infection requiring antibiotic, antifungal or antiviral treatment that, in the opinion of the Investigator, could compromise the patient´s capacity to tolerate the therapy. d) Known active liver (hepatitis B or C or cirrhosis) or renal disease. e) Known human immunodeficiency virus (HIV) infection. f) Major surgery within the two weeks prior to entering the clinical trial or any other concomitant pathology that could jeopardize the patient´s safety or commitment to complete the clinical trial. 9) Pregnant or breastfeeding women. 10) Inability or refusal to comply with the protocol or with the clinical trial procedures. 11) Known hypersensitivity to PM060184 or any of the drugs to be used in the PSPC arm (second stage).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To Evaluate the efficacy of PM060184 in terms of progression-free survival at 4 months (PFS4) in third or fourth line setting in the subset population of advanced, hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative, breast carcinoma;Secondary Objective: Evaluate the feasibility of administering PM060184 in shorter administration times. Evaluate (OS), median (PFS), (ORR) and (DR), as defined by RECIST. Characterize the safety profile and feasibility of PM060184 treatment in this population. Describe the peripheral neuropathy profile at (BL) and over time using a patient reported outcome questionnaire (the EORTC-QLQ-CIPN20). Characterize the (PK) of PM060184 in this subset of patients. Characterize the metabolomics of PM060184, i.e., systemic variations in the patients pre- and post-treatment metabolic profile that allow the identification of potential biomarkers of PK, safety and/or efficacy response to PM060184. Characterize the (PGt) of PM060184, i.e., the presence or absence of germline mutations or polymorphisms that may help explain individual variability in the main PK parameters and safety outcomes.?Analyze the (PGx) of PM060184, i.e., potential predictive factors of sensitivity/resistance to PM060184 treatment.;Primary end point(s): For efficacy if they are eligible and have received at least one treatment cycle with PM060184/PSPC and have undergone at least one radiological post-BL evaluation (performed a minimum of eight weeks ± 1 week from the first drug administration).;Timepoint(s) of evaluation of this end point: Along the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy, Safety, Peripheral neurophaty, Pharmacokinetics, Metabolomic, Pharmacogenetic, Pharmacogenomic;Timepoint(s) of evaluation of this end point: Along the study | — |
Countries
Belgium, Spain
Contacts
Public ContactClinical Trials
Pharma Mar S.A., Sociedad Unipersonal
Outcome results
None listed