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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by PharmaMar
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: January 30, 2012
Last updated: April 26, 2016
Last verified: April 2016
A Clinical Trial of PM01183 in Metastatic Breast Cancer to assess the antitumor activity of PM01183 ,to evaluate whether the presence of a known germline mutation in BRCA 1/2 predicts response to PM01183 in Metastatic Breast Cancer (MBC) patients, to evaluate the safety profile of this PM01183 to analyze the pharmacokinetics (PK) and PK/PD (pharmacokinetic/pharmacodynamic) correlations and to evaluate the pharmacogenomic (PGx) expression profile in tumor samples.

Condition Intervention Phase
Breast Cancer
Drug: PM01183
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by PharmaMar:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment ] [ Designated as safety issue: No ]
    The overall response rate is defined as the percentage of patients with a confirmed response, either complete response or partial response, according to RECIST(Response Evaluation Criteria In Solid Tumors)v1.1.

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the period of time from the date of first infusion to the date of progression disease, death (due to any cause), or last tumor evaluation.

  • Overall survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Overall survival rate at one year is defined as the estimated probability of patients to remain alive at one year. Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact

Estimated Enrollment: 110
Study Start Date: December 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PM01183 Drug: PM01183
PM01183 drug product (DP) is presented as a lyophilized powder for concentrate for solution for infusion with two strengths: 1 mg/vial and 4 mg/vial

Detailed Description:
A Multicenter Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer to assess the antitumor activity of PM01183 in terms of overall response rate (ORR), duration of response (DR),clinical benefit [ORR or stable disease lasting over three months (SD > 3 months)], progression free survival (PFS), and one-year overall survival (1y-OS) and to evaluate whether the presence of a known germline mutation in BRCA 1/2 predicts response to PM01183 in MBC patients, to explore the activity of PM01183 in specific breast cancer subpopulations according to hormonal receptor status, HER-2 overexpression, number and/or type of prior therapies, or according to other available histological/molecular classifications, to evaluate the safety profile of this PM01183 administration schedule [Day 1 every three weeks (q3wk)] in this patient population, to analyze the pharmacokinetics (PK) of PM01183 in this patient population, to explore PK/PD (pharmacokinetic/ pharmacodynamic) correlations, if applicable and to evaluate the pharmacogenomic (PGx) expression profile of selected putative markers potentially predictive of response to PM01183, in tissues from archived tumor samples.

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Women ≥ 18 and ≤ 75 years of age.
  • Voluntary signed informed consent form (ICF).
  • Proven diagnosis of metastatic breast cancer (MBC).
  • At least one, but no more than three, prior chemotherapy regimens for MBC.
  • Patients with known HER-2 overexpressing MBC must have failed at least one prior trastuzumab-containing regimen for metastatic disease.
  • Disease evaluable for response by specific appropriate criteria.
  • No or minimal disease-related symptoms not affecting patient daily activities.
  • Adequate major organ function (normal or minimal alteration in liver, kidney, hematological, metabolic and cardiac function)
  • Wash out periods prior to Day 1 of Cycle 1:

At least three weeks since the last chemotherapy (six weeks in some particular cases) and At least four weeks since the last radiotherapy (RT) > 30 Gy) and At least one week since the last hormonal therapy and At least two weeks since the last biological/investigational therapy

  • Minimal or no ongoing toxicity from immediately prior therapy according to specific appropriate criteria. Mild ongoing toxicity is allowed in case of alopecia, skin toxicity, fatigue and/or finger numbness or tumbling.
  • Patients of child-bearing potential must agree to use a medically approved contraception method until at least six weeks after the last study drug administration.
  • Known deleterious germline mutation of BRCA1/2 (Patients in Cohorts A and A1)
  • Prior treatment with PARP inhibitors (Patients in Cohort A1)

Exclusion Criteria:

  • Prior treatment with PM01183 or trabectedin.
  • Extensive prior RT.
  • Prior or concurrent malignant disease unless cured for more than five years.
  • Exceptions are breast cancer in the other breast.
  • Uncommon or rare subtypes of breast cancer.
  • Symptomatic or progressive brain metastases.
  • Bone-limited and exclusively metastases.
  • Relevant diseases or clinical situations which may increase patient's risk:

History of cardiac disease. Moderate breathing difficulties or oxygen requirement Active uncontrolled infection. Unhealed wound or presence of any external drainage. Chronically active viral hepatitis. Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV).

Known muscular disease or functional alteration

  • Pregnant or breastfeeding women.
  • Impending need for immediate RT for symptomatic relief.
  • Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525589

Contact: Cristian Fernández, MD clinicaltrials@pharmamar.com

United States, California
8 Recruiting
Stanford, California, United States
United States, Massachusetts
2 Recruiting
Boston, Massachusetts, United States, 02114
United States, New York
11 Recruiting
New York, New York, United States
United States, Pennsylvania
7 Recruiting
Philadelphia, Pennsylvania, United States
United States, Texas
10 Recruiting
Houston, Texas, United States
Sponsors and Collaborators
  More Information

Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT01525589     History of Changes
Other Study ID Numbers: PM1183-B-003-11 
Study First Received: January 30, 2012
Last Updated: April 26, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by PharmaMar:
Breast cancer
Pharma Mar

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on May 25, 2016