| Eligibility |
Inclusion Criteria:
- 1. Voluntary written informed consent of the patient.
- 2. Age=18 years.
- 3. Escalating stage: Patients with histologically/cytologically confirmed diagnosis of
advanced solid tumors refractory to standard therapy or for whom refuses or cannot
tolerate standard treatment or no standard therapy exist (no more than three prior
regimens for advanced or unresectable disease).
- 4. Expansion stage: Patients with histologically confirmed diagnosis of advanced or
unresectable SCLC who had failure to one prior platinum -containing line.
- 5. Measurable disease as defined by the RECIST v.1.1.
- 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2.
- 7. Life expectancy =3 months.
- 8. Adequate bone marrow, renal, hepatic, and metabolic function as follows: Platelet
count = 100 x 109/l, Hemoglobin = 90 g/l, absolute neutrophil count (ANC) = 2.0 x
109/l; Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 3.0 x
upper limit of normal (ULN), = 5.0 x ULN if presence of liver metastases; Alkaline
phosphatase = 5.0 x ULN ; Total bilirubin = 1.5 x ULN, and direct bilirubin =1 x ULN ;
Serum creatinine = 1.5 x ULN or Calculated creatinine clearance: = 30 ml/min
(calculated using the Cockcroft and Gault formula); Creatine phosphokinase (CPK) = 2.5
x ULN; Albumin = 3 g/dl.
- 9. Recovery to grade = 1 according to the NCI-CTCAE v.5.0, of any ongoing adverse
event derived from previous treatment ( with the exception of grade 2 alopecia and
non-painful peripheral sensory neuropathy ).
- 10. Women of childbearing potential must have a negative serum pregnancy test before
study entry. Women of childbearing potential must agree to use a medically acceptable
method of contraception throughout the treatment period and for 6 months after
discontinuation of treatment. Male patients (female partners is of childbearing
potential ) take effective contraceptive measures throughout the treatment period and
for 4 months after discontinuation of treatment.
Exclusion Criteria:
- 1. Prior treatment with trabectedin.
- 2. Patients with brain metastases, a history of spinal cord compression, or meningeal
metastases.
- 3. Suspected or confirmed disease bone marrow involved.
- 4. Bone metastases, obstructive atelectasis, superior vena cava syndrome patients with
local symptoms that may require radiotherapy/surgery/endoscopic
treatment/interventional intervention; patients with suspected or confirmed pulmonary
embolism; uncontrollable large amounts of pleural fluid, ascites and pericardial
effusion.
- 5. Patients who received other recent antitumor therapies ( with respect to study
treatment start ) : Less than three weeks since the last chemotherapy-containing
regimen (six weeks in case of nitrosoureas, mitomycin C ).
Less than four weeks since the last monoclonal antibody-containing therapy or radiotherapy
(RT) dose >30 Gy.
Less than two weeks since the last any other biological/investigational anticancer therapy
or palliative radiotherapy ( total dose =30 Gy).
- 6. Concomitant diseases/conditions: History (during the last year) or presence of any
of the following: unstable angina, myocardial infarction, New York Heart Association
(NYHA) Class II or greater congestive heart failure (CHF), or clinically significant
valvular heart disease; History of stroke within 1 year (including ischemic stroke,
hemorrhagic stroke); Patients with uncontrolled hypertension (systolic blood pressure
greater than 160 mmHg and/or diastolic blood pressure greater than 100 mmHg); History
of hypertensive crisis or hypertensive encephalopathy; Severe arrhythmia requiring
ongoing pharmacological treatment; Positive tests for Hepatitis B surface antigen
(HBsAg) and the peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA)
titer test is =1×103 copies/mL; if the HBsAg is positive, and the peripheral blood HBV
DNA titer test is <1×103 copies/ml and in the Investigator's judgment, the patient is
under a stable stage of chronic hepatitis B and does not increase the risk of the
patient, then the patient is eligible for selection; HCV antibody positive or HIV
antibody positive; Active uncontrolled infection requiring ongoing medical treatment
within two weeks prior to treatment start.
Evidence of bleeding diathesis or significant coagulopathy; Prior or concurrent invasive
malignancy other than the primary study indication within 5 years prior to treatment start,
except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin
cancer, local prostate cancer after radical resection, and ductal carcinoma in situ after
radical resection; Any other major illness that, in the Investigator's judgment, not
suitable for inclusion in this study.
- 7. History of previous bone marrow and/or stem cell transplantation.
- 8. Prior medication requirements: Patients who have used strong inducers or inhibitors
of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks or 5 half-lives ( whichever is
longer ) prior to treatment start; Prophylaxis or treatment for non-febrile
neutropenia with G-CSF within two weeks prior to treatment start; Patients who have
used erythropoietin and derivatives within 3 weeks prior to treatment start; Patients
who have used blood transfusions within 2 weeks prior to treatment start.
- 9. Patients who may need to receive other systemic anti-tumor or radical treatments
for local target/non-target lesions during the study period;
- 10. Known history of psychotropic drug, alcohol or drug abuse;
- 11. Known to be allergic to any component of the investigational drug;
- 12. Pregnant or breastfeeding women, or women of childbearing potential have a
positive blood pregnancy test.
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