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

Luye Pharma Group Ltd.1 site in 1 country32 target enrollmentNovember 24, 2020

ConditionsAdvanced Solid Tumor

InterventionsLurbinectedin for injection

DrugsLurbinectedin for injection

Overview

Phase: Phase 1
Intervention: Lurbinectedin for injection
Conditions: Advanced Solid Tumor
Sponsor: Luye Pharma Group Ltd.
Enrollment: 32
Locations: 1
Primary Endpoint: Objective Response Rate(ORR)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

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

Registry

clinicaltrials.gov

Start Date

November 24, 2020

End Date

November 4, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Luye Pharma Group Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Voluntary written informed consent of the patient.
•Age≥18 years.
•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).
•Expansion stage: Patients with histologically confirmed diagnosis of advanced or unresectable SCLC who had failure to one prior platinum -containing line.
•Measurable disease as defined by the RECIST v.1.
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
•Life expectancy ≥3 months.
•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.
•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 ).
•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

•Prior treatment with trabectedin.
•Patients with brain metastases, a history of spinal cord compression, or meningeal metastases.
•Suspected or confirmed disease bone marrow involved.
•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.
•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).
•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.
•History of previous bone marrow and/or stem cell transplantation.

Arms & Interventions

single-arm

PM01183-Dose Escalation

Intervention: Lurbinectedin for injection

Outcomes

Primary Outcomes

Objective Response Rate(ORR)

Time Frame: 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)

The number and percentage of subjects with significant remission (CR + PR) were calculated, and the 95% confidence interval of the percentage was calculat

Secondary Outcomes

Duration of remission (DOR)(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)(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)(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))
Disease Control Rate(DCR)(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))