Selected Advanced Solid Tumors. MedDRA version: 18.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Sponsors
Pharma Mar S.A. Sociedad Unipersonal
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Age ? 18 years. 2)Voluntary signed informed consent (IC) of the patient before any study-specific procedure. 3)Pathologically proven diagnosis of any of the following malignancies: a)Small cell lung cancer (SCLC). b)Head and neck carcinoma (H&N). Salivary glands and oropharynx carcinoma are excluded. c)Neuroendocrine tumors (NETs), excluding carcinoid tumors. d)Biliary tract carcinoma. e)Endometrial carcinoma. f)BRCA 1/2-associated metastatic breast carcinoma, g)Carcinoma of unknown primary site. h)Germ cell tumor (GCTs), excluding pure teratocarcinoma. i)Ewing?s family of tumors (EFTs). 4)Prior treatment. Patients must have received: a)SCLC: one prior chemotherapy-containing line. b)H&N: one or two prior chemotherapy-containing lines. c)NETs: one prior chemotherapy-containing line. No more than three prior hormone or biological therapy lines. d)Biliary tract carcinoma: one prior chemotherapy-containing line. e)Endometrial carcinoma: one prior chemotherapy-containing line. f)BRCA 1/2-associated metastatic breast carcinoma: at least one but no more than three prior chemotherapy containing lines. g)Carcinoma of unknown primary site: one or two prior chemotherapy-containing lines. h)GCTs: no limit of prior therapy (patients with no other clinical therapeutic options). i)EFTs: two prior chemotherapy-containing lines. 5)Measurable disease as defined by RECIST v.1.1, and documented progression before study entry. 6)Eastern Cooperative Oncology Group (ECOG) performance status (PS) ? 2. 7)Adequate major organ function: a)Hemoglobin ? 9 g/dl, prior red blood cell (RBC) transfusions are allowed 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). c)Total bilirubin ? 1.5 x ULN, or direct bilirubin ? ULN. d)Albumin ? 3 g/dl. e)Serum creatinine ? 1.5 x ULN. f)Creatine phosphokinase (CPK) ? 2.5 x ULN. 8)Washout periods prior to Day 1 of Cycle 1: a)At least three weeks since the last chemotherapy (six weeks if therapy contained nitrosureas or systemic mitomycin C). b)At least four weeks since the last monoclonal antibody (MAb)-containing therapy, or radiotherapy (RT) > 30 gray (Gy). c)At least two weeks since the last biological/investigational therapy (excluding MAbs) or palliative RT (? 10 fractions or ? 30 Gy total dose). 9)Grade ? 1 toxicity due to any previous cancer therapy according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.4). Grade 2 is allowed in case of alopecia and/or peripheral sensory neuropathy. 10)Women of childbearing potential must have pregnancy excluded by appropriate testing before study entry. Fertile women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation. 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 95 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 130
Exclusion criteria
Exclusion criteria: 1)Prior treatment with PM01183 or trabectedin. 2)Prior or concurrent malignant disease unless in complete remission for more than five years, except treated in situ carcinoma of the cervix, basal or squamous cell skin carcinoma, and in situ transitional cell bladder carcinoma. 3)Known central nervous system (CNS) involvement. In patients with SCLC, brain computed tomography (CT)-scan results must be provided at baseline. 4)Relevant diseases or clinical situations which may increase the patient?s risk: a)History within the last year or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically relevant valvular heart disease or symptomatic arrhythmia or any asymptomatic ventricular arrhythmia requiring ongoing treatment. b)Grade ? 3 dyspnea or daily intermittent oxygen requirement within two weeks prior to the study treatment onset. c)Active infection. d)Unhealed wounds or presence of any external drainage. e)Known chronic active hepatitis or cirrhosis. f)Immunocompromised patients, including known infection by human immunodeficiency virus (HIV). 5)Pregnant or breastfeeding women. 6)Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression). 7)Limitation of the patient?s ability to comply with the treatment or to follow-up the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the antitumor activity of lurbinectedin (PM01183) in terms of overall response rate (ORR), according to RECIST v 1.1 in the following advanced solid tumors: small cell lung cancer (SCLC), head and neck carcinoma (H&N), neuroendocrine tumors (NETs), biliary tract carcinoma, endometrial carcinoma, BRCA 1/2-associated metastatic breast carcinoma, carcinoma of unknown primary site, germ cell tumors (GCTs) and Ewing´s family of tumors (EFTs).;Secondary Objective: *Characterize the antitumor activity of PM01183 in terms of duration of response (DR), clinical benefit (ORR or stable disease (SD) lasting over four months (SD>=4 months)), progression-free survival (PFS) and one-year overall survival (1y-OS) in each cohort of advanced solid tumors. *Characterize the plasma pharmacokinetics (PK) of PM01183. *Conduct an exploratory pharmacogenomic (PGx) and pharmacogenetic analysis. *Evaluate the safety profile of PM01183 in this patient population.;Primary end point(s): Overall Response Rate (ORR) in each tumor type. ORR is defined as the percentage of patients with a confirmed response, either complete (CR) or partial (PR), according to the RECIST (v. 1.1).;Timepoint(s) of evaluation of this end point: Along the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Along the study.;Secondary end point(s): Efficacy: ?Duration of Response (DR), defined as the time between the date when the response criteria (PR or CR, whichever one is first reached) are fulfilled to the first date when PD, recurrence or death is documented. ?Clinical Benefit, defined as ORR or stable disease lasting over four months (SD ? 4 months). ?Progression-free Survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (of any cause), or last tumor evaluation. ?PFS4/PFS6, defined as the Kaplan-Meier estimates of the probability of being free from progression and death after the first infusion at these time points (4 and 6 months). ?OS6/OS12, defined as the Kaplan-Meier estimates of the probability of being alive after the first infusion at these time points (6 and 12 months). Plasma Pharmacokinetics (PK) of PM01183 Non-compartmental (NCA) PK parameters: area under the curve (AUC), maximum plasma concentration (Cmax), clearance (CL) and half-life (t1/2). Population PK parameters of the compartment model to be developed (initially based on Volumes and Clearance), and PK/PD correlation parameters, if applicable. Pharmacogenetics This analysis will be performed in those patients who signed the IC for the pharmacogenetic sub-study. The presence or absence of known polymorphisms from a single sample collected just before the PM01183 treatment start will be assessed to explain the individual variability in the main PK parameters. Pharmacogenomics (PGx): This exploratory analysis will be performed in those patients treated in any arm who signed the IC for the PGx sub-study. mRNA or protein expression levels of factors involved in DNA repair mechanisms, or related to the mechanism of action of lurbinectedin, will be evaluated from prior available tumor tissue samples obtained at diagnosis or relapse. Their mutational status might be also analyzed. Their correlation with | — |
Countries
Belgium, Germany, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trials
Pharma Mar, S.A. Sociedad Unipersonal
Outcome results
None listed