Description:
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.
Title
- Brief Title: A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer
- Official Title: A Multicenter Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
PM1183-B-003-11
- NCT ID:
NCT01525589
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| PM01183 | | PM01183 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| PM01183 | Experimental | | |
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.
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| 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 |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression-free Survival (PFS) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival (OS) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | PharmaMar |
Trial Keywords
- Breast cancer
- PM01183
- lurbinectedin
- Pharma Mar
Last Updated
September 25, 2020
