Back to resultsA 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
Primary Purpose
Non-Small Cell Lung Cancer (NSCLC)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Docetaxel
Gemcitabine
Lurbinectedin (PM01183)
Sponsored by
About this trial
This is an interventional treatment trial for 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
A - docetaxel
B - lurbinectedin (PM01183)
C - gemcitabine + lurbinectedin (PM01183)
Arm Description
75 mg/m2 docetaxel day 1, 1-hour intravenous, every three weeks
3.2 mg/m2 PM01183, day 1, 1-hour intravenous, every three weeks
800 mg/m2 gemcitabine / 1.6 mg/m2 PM01183 both on day 1 and day 8, 30-minutes gemcitabine/1-hour PM01183 intravenous, every three weeks
Outcomes
Primary Outcome Measures
Progression-free Survival Rate at Four Months (PFS4)
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.
Secondary Outcome Measures
Progression-free Survival
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.
Progression-free Survival Rate at Six Months (PFS6)
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.
Overall Response Rate
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.
Objective Response Per RECIST v.1.1
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
Duration of Response
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.
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
Information on Quality of Life (QoL)
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01951157
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
September 11, 2013 (Actual)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PharmaMar
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer (NSCLC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A - docetaxel
Arm Type
Active Comparator
Arm Description
75 mg/m2 docetaxel day 1, 1-hour intravenous, every three weeks
Arm Title
B - lurbinectedin (PM01183)
Arm Type
Experimental
Arm Description
3.2 mg/m2 PM01183, day 1, 1-hour intravenous, every three weeks
Arm Title
C - gemcitabine + lurbinectedin (PM01183)
Arm Type
Experimental
Arm Description
800 mg/m2 gemcitabine / 1.6 mg/m2 PM01183 both on day 1 and day 8, 30-minutes gemcitabine/1-hour PM01183 intravenous, every three weeks
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Powder for solution for infusion
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Powder for solution for infusion
Intervention Type
Drug
Intervention Name(s)
Lurbinectedin (PM01183)
Intervention Description
Powder for concentrate for solution for infusion
Primary Outcome Measure Information:
Title
Progression-free Survival Rate at Four Months (PFS4)
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.
Time Frame
At month four after patient inclusion
Secondary Outcome Measure Information:
Title
Progression-free Survival
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.
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
Title
Progression-free Survival Rate at Six Months (PFS6)
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.
Time Frame
At month six after patient inclusion
Title
Overall Response Rate
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.
Time Frame
Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
Title
Objective Response Per RECIST v.1.1
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
Time Frame
Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
Title
Duration of Response
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.
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
Title
Overall Survival (OS)
Description
Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact
Time Frame
From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion
Title
Information on Quality of Life (QoL)
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)
Time Frame
Baseline, Cycle 3 (~9 weeks), Cycle 6 (~18 weeks) and Cycle 9 (~27 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
City
New York
State/Province
New York
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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