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

NCT04638491 | Completed Phase 1

• 1 other identifier: LY01017/CT-CHN-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Conditions

Advanced Solid Tumor

Keywords

Lurbinectedin(PM01183) for injection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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)

• 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)

• 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)

Study Arms (1)

single-arm

EXPERIMENTAL

PM01183-Dose Escalation

Drug: Lurbinectedin for injection

Interventions

Lurbinectedin for injection DRUG

On the first day of each cycle, patients with advancedsolid tumors or small cell lung cancer were treated with Lurbinectedin for injection

Also known as: PM01183

single-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.1.1.
• \. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• \. 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.

You may not qualify if:

• \. 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.
• \. History of previous bone marrow and/or stem cell transplantation.
• \. 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.
• \. Patients who may need to receive other systemic anti-tumor or radical treatments for local target/non-target lesions during the study period;
• \. Known history of psychotropic drug, alcohol or drug abuse;
• \. Known to be allergic to any component of the investigational drug;
• \. Pregnant or breastfeeding women, or women of childbearing potential have a positive blood pregnancy test.

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead

Study Sites (1)

Jilin Provincial Tumor Hospital

Changchun, Jilin, China

Location

Related Publications (1)

• Cheng Y, Wu C, Wu L, Zhao J, Zhao Y, Chen L, Xin Y, Zhang L, Pan P, Li X, Li J, Dong X, Tang K, Gao E, Yu F. A pivotal bridging study of lurbinectedin as second-line therapy in Chinese patients with small cell lung cancer. Sci Rep. 2024 Feb 13;14(1):3598. doi: 10.1038/s41598-024-54223-5.

  PMID: 38351146 DERIVED

MeSH Terms

Interventions

PM 01183; Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• cheng ying, Doctor

  Jilin Provincial Tumor Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Lurbinectedin for injection(PM01183)

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 20, 2020
• Study Start: November 24, 2020
• Primary Completion: November 4, 2023
• Study Completion: November 4, 2023
• Last Updated: June 10, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)