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

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ClinicalTrials.gov Identifier: NCT01525589
Recruitment Status : Completed
First Posted : February 3, 2012
Results First Posted : September 25, 2020
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Tracking Information
First Submitted Date  ICMJE January 30, 2012
First Posted Date  ICMJE February 3, 2012
Results First Submitted Date  ICMJE July 20, 2020
Results First Posted Date  ICMJE September 25, 2020
Last Update Posted Date September 25, 2020
Actual Study Start Date  ICMJE June 13, 2012
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2020)
  • 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 ]
    The overall response rate is defined as the percentage of patients with a confirmed response, either complete response (CR) or partial response (PR), according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR >=30% decrease in the sum of the longest diameter of target lesions.
  • Overall Response [ Time Frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment ]
    Overall Response Rate (ORR) in the population evaluable for efficacy according to RECIST v.1.1. ORR was defined as the percentage of patients with a confirmed response, either CR or PR, according to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: >=30% decrease in the sum of the longest diameter of target lesions; SD, stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; TF, treatment failure.
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2012)
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 ]
The overal 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2020)
  • Duration of Response [ Time Frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment ]
    Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: >=30% decrease in the sum of the longest diameter of target lesions.
  • Duration of Response Rate at 6 Months [ Time Frame: Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 6 months ]
    Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: >=30% decrease in the sum of the longest diameter of target lesions.
  • Duration of Response Rate at 12 Months [ Time Frame: Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 12 months ]
    Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: >=30% decrease in the sum of the longest diameter of target lesions.
  • Clinical Benefit Rate [ Time Frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment ]
    Clinical benefit, defined as the percentage of patients with ORR or SD lasting over three months (SD >3 months). The overall response rate is defined as the percentage of patients with a confirmed response, either complete response (CR) or partial response (PR), according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR >=30% decrease in the sum of the longest diameter of target lesions. SD, stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
  • Progression-free Survival (PFS) [ Time Frame: 36 months ]
    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. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
  • Progression-free Survival at 3 Months [ Time Frame: Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 3 months ]
    Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
  • Progression-free Survival at 6 Months [ Time Frame: Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 6 months ]
    Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
  • Progression-free Survival at 12 Months [ Time Frame: Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 12 months ]
    Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
  • Overall Survival (OS) [ Time Frame: 36 months ]
    Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact
  • Overall Survival Rate at 12 Months [ Time Frame: Time from the date of first infusion to the date of death or last contact, up to 12 months ]
    Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact
  • Overall Survival Rate at 18 Months [ Time Frame: Time from the date of first infusion to the date of death or last contact, up to 18 months ]
    Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2012)
  • Progression-free Survival (PFS) [ Time Frame: 36 months ]
    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 ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer
Official Title  ICMJE A Multicenter Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: PM01183
Intervention: Drug: PM01183
Publications * Cruz C, Llop-Guevara A, Garber JE, Arun BK, Pérez Fidalgo JA, Lluch A, Telli ML, Fernández C, Kahatt C, Galmarini CM, Soto-Matos A, Alfaro V, Pérez de la Haza A, Domchek SM, Antolin S, Vahdat L, Tung NM, Lopez R, Arribas J, Vivancos A, Baselga J, Serra V, Balmaña 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. Erratum in: J Clin Oncol. 2018 Nov 20;36(33):3348. J Clin Oncol. 2019 Feb 1;37(4):362.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 27, 2017)
111
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2012)
117
Actual Study Completion Date  ICMJE October 2018
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01525589
Other Study ID Numbers  ICMJE PM1183-B-003-11
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PharmaMar
Study Sponsor  ICMJE PharmaMar
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PharmaMar
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP