Safety Tolerability Pharmacokinetic and Preliminary Efficacy in Chinese Advanced Solid Tumors Patients

Study Overview
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Brief Summary
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Phase 1, single-arm, open-label, dose escalating and expansion clinical trial to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of Lurbinectedin (PM01183) for injection in patients with advanced solid tumors

Detailed Description
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To evaluate the safety and tolerability of PM01183 as a single agent, and to identify the dose limiting toxicities (DLTs), determine the recommended dose (RD) in Chinese advanced solid tumors patients

Official Title
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Phase 1, Single-arm, Open-label, Dose Escalating and Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic and Preliminary Efficacy of Lurbinectedin (PM01183) for Injection in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: Lurbinectedin for injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Lurbinectedin for injection(PM01183)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single-arm<br>PM01183-Dose Escalation | Drug: Lurbinectedin for injection<br>* On the first day of each cycle, patients with advancedsolid tumors or small cell lung cancer were treated with Lurbinectedin for injection<br>* Other names: PM01183;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | The number and percentage of subjects with significant remission (CR + PR) were calculated, and the 95% confidence interval of the percentage was calculat | From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months(each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate(DCR) | The number and percentage of subjects with disease control (CR+PR+SD) were calculated, and the 95% confidence interval of the percentage was calculated | From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months(each cycle is 21 days) | 
| Progression Free Survival(PFS) | Survival analysis (Kaplan Meier method) was used to estimate the median dor and its 95% confidence interval (CI), and the K-M curve was drawn | From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months(each cycle is 21 days) | 
| Overall Survival(OS) | Survival analysis (Kaplan Meier method) was used to estimate the median dor and its 95% confidence interval (CI), and the K-M curve was drawn | From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months(each cycle is 21 days) | 
| Duration of remission (DOR) | Survival analysis (Kaplan Meier method) was used to estimate the median dor and its 95% confidence interval (CI), and the K-M curve was drawn | From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months(each cycle is 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lurbinectedin(PM01183) for injection