Unresectable Non-Small Cell Lung Cancer (NSCLC). MedDRA version: 14.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Pharma Mar S.A. Sociedad Unipersonal
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Voluntary written IC of the patient obtained before any study-specific procedure. 2) Histologically or cytologically confirmed unresectable NSCLC. 3) Patients must have failed one prior line of CT-based therapy for unresectable disease. 4) Age between 18 and 75 years, both inclusive. 5) Measurable disease as defined by RECIST v1.1. 6) Eastern Cooperative Oncology Group (ECOG) performance status (PS) ? 1. 7) Adequate hematological, renal, metabolic and hepatic function: a) Hemoglobin ? 9 g/dl (patients may have received prior red blood cell [RBC] transfusion up to 48 hours before treatment start, if clinically indicated), absolute neutrophil count (ANC) ? 2.0 x 109/l, and platelet count ? 100 x 109/l. b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? 3.0 x upper limit of normal (ULN) (? 5.0 x ULN if liver metastases are present). c) Total bilirubin ? ULN, or direct bilirubin ? ULN if total bilirubin is > ULN. d) Albumin ? 3.0 g/dl. e) Calculated creatinine clearance (CrCl) ? 30 ml/minute (using Cockcroft and Gault?s formula). f) Creatine phosphokinase (CPK) ? 2.5 x ULN. 8) At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy and recovery to grade ? 1 from any adverse event (AE) derived from previous anticancer treatment, except alopecia, sensory neuropathy, anemia or asthenia (all of which must have recovered to grade ? 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.4). 9) Pre-menopausal women must have a negative pregnancy test before treatment start, not be breast feeding and agree to use adequate contraception during the whole length of study participation and for at least six weeks after the last study dose of PM01183. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1) Concomitant diseases/conditions: a) History (within the last year) or presence of unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic with left ventricular ejection fraction (LVEF) ? 50% (assessed by multiple-gated acquisition scan [MUGA] or equivalent by ultrasound [US]) or clinically significant valvular heart disease. b) Patients with dyspnea at rest or requiring any oxygen support within the last four weeks. c) Known infection by human immunodeficiency virus (HIV), including seropositive patients without AIDs. d) Chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. e) Active uncontrolled infection; patients undergoing active antibiotherapy for an ongoing infection must have finished treatment at least one week before treatment start. f) Pleural or pericardial effusions requiring invasive management procedures. g) Known myopathy of any cause. h) Limitation of the patient?s ability to comply with the treatment or to follow-up the protocol. I) Any other major illness that, in the Investigator?s judgment, will substantially increase the risk associated with the patient?s participation in this study. 2) More than one prior line of CT for advanced or unresectable disease. 3) Histological features of neuroendocrine or bronchioalveolar differentiation. 4) Unknown epidermal growth factor receptor (EGFR) mutation status or previously known EGFR mutated status in patients with adenocarcinoma. 5) Prior or concurrent invasive malignant disease, unless in complete remission for more than three years. Exceptions are completely resected or definitively treated squamous cell carcinoma of the cervix or head and neck without lymphatic spread, cutaneous basal cell carcinoma or superficial transitional cell carcinoma of the bladder. 6) Significant cancer-related weight loss (?10%) within four weeks prior to treatment start. 7) Prior treatment with gemcitabine or docetaxel-containing therapy (one full infusion at least completed). 8) Symptomatic, steroid-requiring or progressive CNS involvement. If there is prior or current, known or suspected CNS involvement, clinical stability and lack of radiological progression of lesions should be demonstrated for at least the immediate six weeks before study entry. 9) Ongoing symptomatic paraneoplastic syndromes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: December 2015.;Main Objective: To evaluate the antitumor activity as progression-freesurvival at four months (PFS4) of PM01183 alone or in combination with gemcitabine as second-line treatment in unresectable NSCLC patients, using single agent docetaxel as a reference in the control arm as current standard of care.;Secondary Objective: *To analyze the following in each of the three treatment arms: - Time-to-event endpoints, such as: progression-free survival (PFS), overall survival (OS), overall survival rate at 1-year (OS12) and duration of response (DR). - Antitumor activity, as response rate (RR) evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - Safety and efficacy profiles of PM01183 alone and in combination with gemcitabine, to be preliminary compared with docetaxel. - Patients? quality of life (QoL) assessment. - To explore the feasibility and safety of a PM01183 maintenance dose in non-progressing NSCLC patients. - Pharmacokinetics (PK) of PM01183. - PK/PD (pharmacokinetic/pharmacodynamic) correlation in PM01183-based treated patients, whenever possible. *Pharmacogenomics (PGx): To explore potential correlations between molecular parameters found in previous available tumor samples and clinical outcomes achieved with PM01183-based treatment.;Primary end point(s): Progression-free survival rate at four months (PFS4), defined as the rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (~4 months) after randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate (ORR), Duration of response (DR), Progression-Free Survival (PFS), Overall Survival (OS), Overall Survival rate at 1 year (OS12), Treatment Safety, Quality of Life (QoL), Non-compartmental (NCA) PK parameters, Pharmacogenomics (PGx).;Timepoint(s) of evaluation of this end point: December 2015. | — |
Countries
Belgium, France, Italy, Spain, United States
Contacts
Public ContactClinical Trials
Pharma Mar, S.A. Sociedad Unipersonal
Outcome results
None listed