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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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ClinicalTrials.gov Identifier: NCT01951157
Recruitment Status : Completed
First Posted : September 26, 2013
Results First Posted : September 24, 2019
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer (NSCLC) Drug: Docetaxel Drug: Gemcitabine Drug: Lurbinectedin (PM01183) Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 11, 2013
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Active Comparator: A - docetaxel
75 mg/m2 docetaxel day 1, 1-hour intravenous, every three weeks
Drug: Docetaxel
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Experimental: B - lurbinectedin (PM01183)
3.2 mg/m2 PM01183, day 1, 1-hour intravenous, every three weeks
Drug: Lurbinectedin (PM01183)
Powder for concentrate for solution for infusion

Experimental: C - gemcitabine + 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
Drug: Gemcitabine
Powder for solution for infusion

Drug: Lurbinectedin (PM01183)
Powder for concentrate for solution for infusion




Primary Outcome Measures :
  1. Progression-free Survival Rate at Four Months (PFS4) [ Time Frame: 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 :
  1. Progression-free Survival [ 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 ]
    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.

  2. Progression-free Survival Rate at Six Months (PFS6) [ Time Frame: 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.

  3. Overall Response Rate [ Time Frame: 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.


  4. Objective Response Per RECIST v.1.1 [ Time Frame: 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

  5. Duration of Response [ 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 ]

    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.


  6. Overall Survival (OS) [ Time Frame: 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

  7. Information on Quality of Life (QoL) [ Time Frame: 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)




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01951157


Locations
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United States, New York
New York, New York, United States
Sponsors and Collaborators
PharmaMar

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Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT01951157    
Other Study ID Numbers: PM1183-B-004-13
First Posted: September 26, 2013    Key Record Dates
Results First Posted: September 24, 2019
Last Update Posted: September 24, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Docetaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators