Recurrent or metastatic, unresectable B3 thymoma or thymic carcinoma previously treated with multiple lines of chemotherapy
Conditions
Interventions
Product Name: PHA-848125AC
Product Code: PHA-848125AC
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Milciclib Maleate
CAS Number: 802539-81-7
Current Sponsor code: PHA-848125AC
Concentration
Sponsors
Nerviano Medical Sciences S.r.l.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after more than one prior systemic therapy for advanced / metastatic disease. Note: Any adjuvant and neoadjuvant systemic therapy followed by the recurrence of the disease within 12 months after the start of the adjuvant treatment will be considered as one therapy for advanced / metastatic disease. - Presence of measurable disease. - Age = 18 years with ECOG performance status 0-1. - Use of effective contraceptive methods if man and women of child producing potential. - Adequate hematologic status: Absolute Neutrophils Count = 1,500 cells/mm3, Platelet Count = 100,000 cells/mm3, Hemoglobin = 9.0 g/dL. - Adequate liver function: Total Serum Bilirubin =1.5 x upper limit of normal (ULN), Transaminases (AST/ALT) = 2.5 ULN (if liver metastases are present = 5 ULN), ALP= 2.5 ULN (if liver and/or bone metastases are present = 5 ULN). - Adequate renal function: Serum Creatinine = ULN or Creatinine Clearance calculated by Cockcroft and Gault’s formula > 60 mL/min. - 2 weeks or 5 medication half-lives (whichever is longer) must have elapsed since completion of prior systemic therapy and 2 weeks must have elapsed since completion of prior minor surgery and radiotherapy. - Resolution of all acute toxic effects of any prior chemotherapy, surgery or radiotherapy to NCI CTC (Version 3.0) grade = 1. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Any of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis. - Grade >1 retinopathy as determined by an ophthalmologist. - Known brain metastases. - Known active infections. - Pregnant or breast feeding women. - Diabetes mellitus uncontrolled. - Gastrointestinal disease (e.g. Crohn’s disease, ulcerative colitis, or short gut syndrome) that would impact on drug absorption. - Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at baseline. - Patients with previous history or current presence of neurological disorders (with the exception of myasthenia gravis), including epilepsy (although controlled by anticonvulsant therapy), Parkinson’s disease and extra-pyramidal syndromes. - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of the antitumor activity of PHA-848125AC in patients with recurrent or metastatic, unresectable B3 thymoma or thymic carcinoma who have received more than one line of prior systemic therapy for advanced / metastatic disease. Antitumor activity will be evaluated on the basis of the progression-free survival status at 3 months.;Secondary Objective: • Assessment of additional measures of tumor control to further characterize the efficacy profile of PHA-848125AC in recurrent or metastatic, unresectable B3 thymoma or thymic carcinoma patients who have received more than one line of prior systemic therapy for advanced / metastatic disease. • Evaluation of the safety profile of repeated administrations of PHA-848125AC in patients with recurrent or metastatic, unresectable B3 thymoma or thymic carcinoma who have received more than one line of prior systemic therapy for advanced / metastatic disease. • Exploratory Objective: Relationship of p53, p21, p27, cyclin D1, p75, TRKA and other genes/proteins in tumor biopsies obtained before study entry with treatment efficacy. ;Primary end point(s): Progression-free survival rate at 3 months (PFS-3 rate). The PFS-3 rate, will be calculated as the proportion of evaluable patients known to be alive and progression-free at = 3 months since study treatment start out of the total number of evaluable patients.;Timepoint(s) of evaluation of this end point: 3 months after treatment starts. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective Response Rate 2) Disease Control Rate 3) Progression-free survival 4) Duration of Response 5) Overall Survival (OS 6) Overall safety profile and blood chemistry abnormalities 7) Characterization of selected biomarkers ;Timepoint(s) of evaluation of this end point: 1-5) All study period 6) All cycles from enrollment to 28 days after last treatment 7) At baseline | — |
Countries
Italy, United States
Contacts
Public ContactMarcella Martignoni
CLIOSS S.r.l.
Outcome results
None listed