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

NCT ID: NCT01525589

Last Updated: 2020-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-13
• Study Completion Date: 2018-10-31

Brief Summary

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.

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 tumor samples.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PM01183

Group Type: EXPERIMENTAL

PM01183

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford Women's Cancer Center

Stanford, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Weill Cornell Medical College - New York Presbyterian Hospital

New York, New York, United States

Abramson Cancer Center - Hospital of the University of Pennsylvania at Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Complexo Hospitalario Universitario A Coruña

A Coruña, A Coruña, Spain

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Countries

United States; Spain

References

Fernandez-Teruel C, Lubomirov R, Fudio S. Population Pharmacokinetic-Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin. J Clin Pharmacol. 2021 Sep;61(9):1206-1219. doi: 10.1002/jcph.1886. Epub 2021 Jun 9.

Reference Type: DERIVED

PMID: 33914350 (View on PubMed)

Cruz C, Llop-Guevara A, Garber JE, Arun BK, Perez Fidalgo JA, Lluch A, Telli ML, Fernandez C, Kahatt C, Galmarini CM, Soto-Matos A, Alfaro V, Perez de la Haza A, Domchek SM, Antolin S, Vahdat L, Tung NM, Lopez R, Arribas J, Vivancos A, Baselga J, Serra V, Balmana J, Isakoff SJ. Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy. J Clin Oncol. 2018 Nov 1;36(31):3134-3143. doi: 10.1200/JCO.2018.78.6558. Epub 2018 Sep 21.

Reference Type: DERIVED

PMID: 30240327 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PM1183-B-003-11

Identifier Type: -

Identifier Source: org_study_id