A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer.

Phase 1

Conditions: BRCA1 / BRCA2 associated or unselected Metastatic Breast Cancer.
MedDRA version: 14.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-006108-11-ES

Lead Sponsor: Pharma Mar, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 117

Inclusion Criteria

Women>=18 and <=75 years of age/Voluntary signed informed consent form before any study procedure/Histologically proven diagnosis of metastatic breast carcinoma/ At least one, but no more than three, prior chemotherapy-containing regimens for MBC/Patients with known HER-2 overexpressing tumors must have failed at least one prior trastuzumab-containing regimen for metastatic disease/Measurable disease as defined by RECIST v1.1/ECOG performance status 0 or 1/Adequate major organ function/Wash out periods prior to Day 1 of Cycle 1/Grade <=1 toxicity due to any previous cancer therapy according to NCI-CTCAE/ Patients of child-bearing potental must agree to use a medically approved contraception method until at least six weeks after the last study drug administration.
Patients in Cohort A: Known deleterius germline mutation of BRCA 1/2.
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 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

Prior treatment with PM01183 or trabectedine/Prior RT in more than 35% of the bone marrow/ Prior or concurrent malignant disease unless in complete remission for more than five years/Histology other than ductal or lobulillar carcinoma of the breast/Symptomatic , steroid requiring or progressive central nervous system (CNS) involvement/Exclusively bone-limited disease/Relevant diseases or clinical situations which may increase patient´s risk/ Pregnant or breastfeeding women/ Impending need for RT/Limitation of the patient´s ability to comply with the treatment or to follow-up the protocol.
Patients in Cohort B: Known deleterius germline mutation of BRCA 1/2.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the antitumor activity of PM01183 in terms of overall response rate (ORR) according to RECIST vs 1.1 in each cohort of metastatic breast cancer (MBC) patients.;Secondary Objective: Characterize the antitumor activity of PM01183 in terms of duration of response (DR) clinical benefit, progression free survival (PFS) and one-year overall survival (ly-OS) /Evaluate whether the presence of a known germline mutation in BRCA 1/2 predicts response of PM01183 in MBC patients/Explore activity of PM01183 in specific breast cancer subpopulations/ Evaluate safety profile of PM01183/Explore PK/PD correlations if applicable/Evaluate PGx expression.;Primary end point(s): Overall response rate (ORR), according to RECIST v.1.1, in each cohort of metastatic breast cancer (MBC) patients.;Timepoint(s) of evaluation of this end point: Timepoint (TP): Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Duration of response (DR)/ Clinical benefit, defined as the percentage of patients with ORR or SD> 3 months, according to RECIST v1.1/Progression-free survival (PFS)/ Overall survival rate at one year (1y-OS)/ Treatment safety/PK analysis and PK/PD correlation, if applicable/ PGx expression profile.;Timepoint(s) of evaluation of this end point: Duration of response (DR). TP: 36 months<br>Clinical benefit, defined as the percentage of patients with ORR or SD > 3 months, according to RECIST v1.1. (TP:29-32 months)<br>Progression-free survival (PFS). TP: 36 months<br>Overall survival rate at one year (1y-OS). 36 months<br>Treatment safety: AEs, serious AEs (SAEs) and laboratory abnormalities will be graded according to the NCI-CTCAE (v4). (25-26 months)<br>PK analysis and PK/PD correlation, if applicable. 36 months approximately<br>PGx expression profile, in tissues from archived tumor samples: 36 months