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Breast CancerPhase 2NCT01525589

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

A Phase 2 study testing PM01183 in people with Breast Cancer, run by PharmaMar at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
PM01183
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
9 sitesin 2 countries
Study dates
13 Jun 2012to Oct 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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)

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States5 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Weill Cornell Medical College - New York Presbyterian Hospital

    New York, New York, 10065

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

    Philadelphia, Pennsylvania, 19104

  • Stanford Women's Cancer Center

    Stanford, California, 94305

Other trials in United States

Spain4 sites
  • Complexo Hospitalario Universitario A Coruña

    A Coruña, A Coruña, 15006

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Complexo Hospitalario Universitario de Santiago

    Santiago de Compostela, A Coruña, 15706

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

About this study

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

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.

Read the 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
Being tested
PM01183
Keywords
Breast cancer, PM01183, lurbinectedin, Pharma Mar
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PM01183Drug

    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 groups in NCT01525589
Study groupRoleWhat they receive
PM01183ExperimentalNot described
Receives: Drug: PM01183

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    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.

    Measured: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment

  2. Overall Response

    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.

    Measured: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment

Secondary outcomes (11)
  1. Duration of Response

    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.

    Measured: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment

  2. Duration of Response Rate at 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.

    Measured: Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 6 months

  3. Duration of Response Rate at 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.

    Measured: Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 12 months

  4. Clinical Benefit Rate

    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.

    Measured: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment

  5. Progression-free Survival (PFS)

    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.

    Measured: 36 months

  6. Progression-free Survival at 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.

    Measured: 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

  7. Progression-free Survival at 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.

    Measured: 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

  8. Progression-free Survival at 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.

    Measured: 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

  9. Overall Survival (OS)

    Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact

    Measured: 36 months

  10. Overall Survival Rate at 12 Months

    Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact

    Measured: Time from the date of first infusion to the date of death or last contact, up to 12 months

  11. Overall Survival Rate at 18 Months

    Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact.

    Measured: Time from the date of first infusion to the date of death or last contact, up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2012 (estimated)
  2. Study start13 Jun 2012
  3. Primary completionOct 2018
  4. Study completionOct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01525589
Sponsor's protocol ID
PM1183-B-003-11
Status last verified
Nov 2018
First submitted
30 Jan 2012
Last updated
25 Sep 2020
Data monitoring committee
No

Publications

  • 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.

    PubMed 33914350
  • 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.

    PubMed 30240327

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PM01183 in people with Breast Cancer, run by PharmaMar at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01525589, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2020.

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