Brief Summary
A clinical study of lurbinectedin(PM01183) alone or in combination with gemcitabine in comparison to docetaxel for the treatment of unresectable non-small cell lung cancer (NSCLC)patients
Brief Title
A Clinical Study in Three-arm of Lurbinectedin (PM01183) Alone or in Combination With Gemcitabine and a Control Arm With Docetaxel as Second Line Treatment in Non-Small Cell Lung Cancer (NSCLC) Patients
Detailed Description
A randomized-controlled, three-arm, phase II study of lurbinectedin (PM01183) alone or in combination with gemcitabine and a control arm with docetaxel as second-line treatment in unresectable non-small cell lung cancer (NSCLC)patients to evaluate the antitumor activity as progression-free survival at four months (PFS4) of PM01183 alone or in combination with gemcitabine as using single agent docetaxel as a reference in the control arm as current standard of care and to analyze overall survival (OS), overall survival rate at 1-year (OS12), duration of response (DR), antitumor activity, as response rate (RR), safety and efficacy profiles of PM01183 alone and in combination with gemcitabine, to be preliminary compared with docetaxel, patients' quality of life (QoL), pharmacokinetics (PK) of PM01183, pharmacokinetic/pharmacodynamic (PK/PD)correlation and pharmacogenomics (PGx)to explore potential correlations between clinical outcomes and molecular parameters found in tumor and blood samples
Completion Date
Completion Date Type
Actual
Conditions
Non-Small Cell Lung Cancer (NSCLC)
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed unresectable NSCLC
* Patients must have failed one prior line of CT-based therapy for unresectable disease
* Age between 18 and 75 years
* Eastern Cooperative Oncology Group (ECOG)performance status (PS) ≤ 1
* Adequate hematological, renal, metabolic and hepatic function
* At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy
* Negative pregnancy test for pre-menopausal women
Exclusion Criteria:
* Concomitant diseases/conditions as unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic with left ventricular ejection fraction (LVEF) ≤ 50%, dyspnea, infection by human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active uncontrolled infection, pleural or pericardial effusions, myopathy, limitation of the patient's ability to comply with the treatment or to follow-up the protocol, any other major illness
* Histological features of neuroendocrine or bronchioalveolar differentiation.
* Unknown epidermal growth factor receptor (EGFR)mutation status or previously known EGFR mutated status in patients with adenocarcinoma.
* Prior or concurrent invasive malignant disease, unless in complete remission for more than three years.
* Significant cancer-related weight loss (≥10%)within four weeks prior to treatment start
* Prior treatment with docetaxel-containing therapy
* Symptomatic, steroid-requiring or progressive central nervous system (CNS) involvement
* Paraneoplastic syndromes
* Histologically or cytologically confirmed unresectable NSCLC
* Patients must have failed one prior line of CT-based therapy for unresectable disease
* Age between 18 and 75 years
* Eastern Cooperative Oncology Group (ECOG)performance status (PS) ≤ 1
* Adequate hematological, renal, metabolic and hepatic function
* At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy
* Negative pregnancy test for pre-menopausal women
Exclusion Criteria:
* Concomitant diseases/conditions as unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic with left ventricular ejection fraction (LVEF) ≤ 50%, dyspnea, infection by human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active uncontrolled infection, pleural or pericardial effusions, myopathy, limitation of the patient's ability to comply with the treatment or to follow-up the protocol, any other major illness
* Histological features of neuroendocrine or bronchioalveolar differentiation.
* Unknown epidermal growth factor receptor (EGFR)mutation status or previously known EGFR mutated status in patients with adenocarcinoma.
* Prior or concurrent invasive malignant disease, unless in complete remission for more than three years.
* Significant cancer-related weight loss (≥10%)within four weeks prior to treatment start
* Prior treatment with docetaxel-containing therapy
* Symptomatic, steroid-requiring or progressive central nervous system (CNS) involvement
* Paraneoplastic syndromes
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed unresectable NSCLC
* Patients must have failed one prior line of CT-based therapy for unresectable disease
* Age between 18 and 75 years
* Eastern Cooperative Oncology Group (ECOG)performance status (PS) ≤ 1
* Adequate hematological, renal, metabolic and hepatic function
* At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy
* Negative pregnancy test for pre-menopausal women
* Histologically or cytologically confirmed unresectable NSCLC
* Patients must have failed one prior line of CT-based therapy for unresectable disease
* Age between 18 and 75 years
* Eastern Cooperative Oncology Group (ECOG)performance status (PS) ≤ 1
* Adequate hematological, renal, metabolic and hepatic function
* At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy
* Negative pregnancy test for pre-menopausal women
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT01951157
Org Class
Industry
Org Full Name
PharmaMar
Org Study Id
PM1183-B-004-13
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized-Controlled Three-arm Phase II Study of Lurbinectedin (PM01183) Alone or In Combination With Gemcitabine and a Control Arm With Docetaxel as Second-Line Treatment in Unresectable Non-Small Cell Lung Cancer (NSCLC) Patients
Primary Outcomes
Outcome Description
The rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (\~4 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Outcome Measure
Progression-free Survival Rate at Four Months (PFS4)
Outcome Time Frame
At month four after patient inclusion
Secondary Outcomes
Outcome Description
PFS, progression-free survival Progression-free survival (PFS), defined as the time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Outcome Time Frame
Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years
Outcome Measure
Progression-free Survival
Outcome Description
The rate estimate of the percentage of patients who are alive and progression-free at 24 weeks (\~6 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Outcome Time Frame
At month six after patient inclusion
Outcome Measure
Progression-free Survival Rate at Six Months (PFS6)
Outcome Description
Overall response rate (ORR) was defined as the percentage of patients with a response, either CR or PR, according to RECIST v.1.1.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Outcome Time Frame
Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
Outcome Measure
Overall Response Rate
Outcome Description
RECIST, Response Evaluation Criteria In Solid Tumors Complete Response (CR) Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10mm Partial Response (PR) At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters Progressive Disease (PD) At least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of new lesions was considered PD Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF) Symptomatic deterioration/death due to progression or treatment discontinuation due to treatment-related toxicity occurred before any appropriate tumor assessments had been performed
Outcome Time Frame
Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
Outcome Measure
Objective Response Per RECIST v.1.1
Outcome Description
Duration of response (DR) was defined as the time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Outcome Time Frame
The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years
Outcome Measure
Duration of Response
Outcome Description
Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact
Outcome Time Frame
From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion
Outcome Measure
Overall Survival (OS)
Outcome Description
The mean QoL scores self-reported by patients using the Lung Cancer Symptom Scale (LCSS) at baseline and after the start of the therapy in visits 3 or 6 (+/- 1 visit) and visit 9 for those patients in maintenance therapy.
Higher LCSS scores indicate more severe problems and the scale range is (0-100) Total score was calculated as the mean of the total scores of all nine patient ítems (Appetite, Fatigue, Cough, Dyspnea, Hemoptysis, Pain, Lung cancer symptoms, Normal activities, Global QoL)
Higher LCSS scores indicate more severe problems and the scale range is (0-100) Total score was calculated as the mean of the total scores of all nine patient ítems (Appetite, Fatigue, Cough, Dyspnea, Hemoptysis, Pain, Lung cancer symptoms, Normal activities, Global QoL)
Outcome Time Frame
Baseline, Cycle 3 (~9 weeks), Cycle 6 (~18 weeks) and Cycle 9 (~27 weeks)
Outcome Measure
Information on Quality of Life (QoL)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
DOCETAXEL
GEMCITABINE
PM 01183
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING