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

Phase 2

Completed

• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Interventions: Drug: Docetaxel; Drug: Gemcitabine; Drug: Lurbinectedin (PM01183)

• Registration Number: NCT01951157
• Lead Sponsor: PharmaMar

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

Study Timeline

• Study Start: 2013-09-11
• Study First Submitted: 2013-09-17
• Study First Submitted QC: 2013-09-23
• Study First Posted: 2013-09-26
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Results First Submitted: 2019-05-21
• Status Verified: 2019-09
• Results First Submitted QC: 2019-09-04
• Last Update Submitted: 2019-09-04
• Results First Posted: 2019-09-24
• Last Update Posted: 2019-09-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C - gemcitabine + lurbinectedin (PM01183)	Lurbinectedin (PM01183)	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
A - docetaxel	Docetaxel	75 mg/m2 docetaxel day 1, 1-hour intravenous, every three weeks
B - lurbinectedin (PM01183)	Lurbinectedin (PM01183)	3.2 mg/m2 PM01183, day 1, 1-hour intravenous, every three weeks
C - gemcitabine + lurbinectedin (PM01183)	Gemcitabine	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

Primary Outcome Measures

Name	Time	Method
Progression-free Survival Rate at Four Months (PFS4)	At month four after patient inclusion	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

Name	Time	Method
Overall Response Rate	Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years	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	Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years	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	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	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)	From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion	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)	Baseline, Cycle 3 (~9 weeks), Cycle 6 (~18 weeks) and Cycle 9 (~27 weeks)	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)
Progression-free Survival	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	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)	At month six after patient inclusion	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.