An Exploratory Study of Lurbinectedin With Radiotherapy in Locally-advanced SCLC After First-line Therapy

This exploratory trial aims to determine if it is safe to use radiotherapy and lurbinectedin to treat locally-advanced SCLC after first-line therapy. This study will enroll patients with thoracic disease but no distant metastases after first line treatment failure. Lurbinectedin kills tumor cells by blocks transcription and damages the deoxyribonucleic acid (DNA) of tumor cells, which is similar to the way radiation kills tumor cells. Traditional chemotherapy and radiotherapy is a routine medical treatment for locally-advanced SCLC, but the combination is always toxic. This trial may help understand if treating patients with lurbinectedin and radiotherapy could cause less side effects.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: Lurbinectedin; Radiation: Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

To describe the safety in terms of radiation therapy (RT) in combination with lurbinectedin in patients with locally-advanced SCLC after first-line therapy.

SECONDARY OBJECTIVES:

To evaluate the preliminary efficacy of RT plus lurbinectedin, as assessed by Progression free survival (PFS) and Overall survival (OS).

OUTLINE:

Patients receive 2 cycles of lurbinectedin combined with thoracic radiotherapy followed by 2 cycles of lurbinectedin alone. Patients receive lurbinectedin intravenously (IV) over 1 hour on day 1 of each cycle. G-CSF（Granulocyte Colony-Stimulating Factor） will be used for prophylaxis.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nan Bi, MD; Phone Number: +010 87787692; Email: binan_email@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has fully understood this study, voluntarily signed a written informed consent form, and is able to comply with the requirements and restrictions listed in the informed consent form;
• Age ≥ 18 years, Male/female participants;
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2;
• With pathologically confirmed diagnosis of Limited Stage SCLC(LS-SCLC),with local progression (mainly thoracic progression) after first-line chemotherapy with or without immunotherapy, but without distant metastasis; (Currently immunotherapy + chemotherapy is not the standard treatment for LS-SCLC);
• Has sufficient bone marrow, liver, kidney, and metabolic function, i.e., the functional levels of organs meet the following requirements:
• Platelets (PLT) ≥ 100×10^9/L;
• Hemoglobin (Hb) ≥ 90 g/L;
• Absolute neutrophil (ANC) ≥ 2.0×10^9/L;
• Regardless of whether liver metastasis is present, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0× upper limit of normal (ULN);
• Alkaline phosphatase (ALP) ≤ 5×ULN;
• Total bilirubin (TBIL) ≤ 1.5×ULN, and direct bilirubin ≤ 1.0×ULN;
• Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 30 mL/min (calculated using the Cockcroft-Gault formula);
• Creatine phosphokinase (CPK) ≤ 2.5×ULN;
• Albumin ≥ 3.0 g/dL.
• A female of childbearing potential (FCBP) must have a negative serum pregnancy test prior to study entry. Woman of childbearing potential (WOCBP) must use adequate contraception during the test drug treatment period and for 6 months after the final dose. Male patients (with partners of WOCBP) must use adequate contraception for the duration of study participation, and 4 months after completion of administration.

Exclusion Criteria:

• With concurrent brain metastasis, a history of spinal cord compression, or meningeal metastasis;
• With bone metastases;
• Patients with obstructive atelectasis, superior vena cava syndrome requiring surgical/ endoscopic/ interventional treatment; suspected or confirmed pulmonary embolism patients; those with uncontrollable large amounts of pleural effusion, ascites, or pericardial effusion;
• Patients known to be allergic to any component of the test drug;
• Pregnancy or breastfeeding or WOCBP who has a positive serum pregnancy test;

• Comorbidities Requirements:

  1. Has unstable angina, myocardial infarction, congestive heart failure (CHF) classified as New York Heart Association (NYHA) II or higher, or other clinically significant cardiovascular diseases currently or within the past year prior to screening;
  2. Patients with uncontrolled hypertension (systolic blood pressure greater than 160 mmHg and/or diastolic blood pressure greater than 100 mmHg), or a history of hypertensive crisis or hypertensive encephalopathy;
  3. Patients with severe arrhythmias requiring medication;
  4. Patients with active infections requiring systemic antibacterial, antifungal, or antiviral treatment within 2 weeks prior to administration;
  5. Patients with evidence of bleeding tendencies or coagulation disorders;
  6. Patients with other significant diseases judged unsuitable for entry by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Treatment: Lurbinectedin combined with Thoracic Radiotherapy; Patients receive 2 cycles of lurbinectedin 2.6 mg/m2 combined with thoracic radiotherapy followed by 2 cycles of lurbinectedin 2.6 mg/m2 alone. Patients receive lurbinectedin intravenously (IV) over 1 hour on day 1 of each cycle.	Drug: Lurbinectedin; 2.6 mg/m2 , Given IV, every 21 days; Other Names: PM01183; Zepzelca; Radiation: Radiation Therapy; Thoracic radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events of radio therapy with lurbinectedin	≥grade 4 treatment related adverse events within 30 days of final RT fraction; Any treatment related adverse events leading to dose delays or reductions of lurbinectedin; Any treatment related serious adverse events .	30 days following treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median PFS will be estimated.	From protocol treatment initiation to disease progression or death, assessed up to 24 months
Overall survival (OS)	OS will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median OS will be estimated.	From treatment initiation to death, , assessed up to 24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Nan Bi, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: June 29, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: NCC4493

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No