Study of Irinotecan Liposome Injection as Second-line Regimen in Patients With Small Cell Lung Cancer (SCLC)

A Multicenter, Open-label, Single-arm Phase 2 Study of Irinotecan Liposome Injection in Patients With Small Cell Lung Cancer (SCLC) Who Have Progressed After Platinum-based First-line Therapy

This study is a multicenter, open-label, single-arm phase 2 study of irinotecan liposome injection in patients with small cell lung cancer (SCLC) who have progressed after platinum-based first-line therapy. Subjects will receive irinotecan liposome injection until progression or unacceptable toxicity.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Cancer (SCLC)
• Intervention / Treatment: Drug: irinotecan liposome injection

Detailed Description

Patients with small cell lung cancer who have progressed after platinum-based first-line therapy will be enrolled in this study. Patients will receive irinotecan liposome injection at 70 mg/m^2 intravenously, over 90 min on Days 1 of every 14-day cycle until progression or unacceptable toxicity. Imaging assessments will be conducted every three cycles to evaluate the preliminary efficacy of irinotecan liposome injection as second-line regimen in patients with SCLC.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuekun Yao, Director; Phone Number: +8631169085937; Email: yaoxuekun@mail.ecspc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. At least 18 years of age. Males or females.
2. Histopathologically or cytologically confirmed small cell lung cancer.
3. At least one measurable lesion as defined by RECIST V1.1 guidelines. A previously irradiated lesion may be counted as a measurable lesion only if there is a clear sign of progression since the irradiation.
4. Must have recurrence or progression after platinum-based, first-line chemotherapy or chemoradiation therapy for the treatment of SCLC.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy >3 months.
7. Recovered from the effects of any prior chemotherapy, surgery, radiotherapy or other anti-neoplastic therapy (recovered to no more than Grade 1 of CTCAE 5.0 criteria or baseline, with the exception of alopecia or other toxicity without safety concerns by the investigators' judgment).
8. Patient should not receive blood transfusion or supportive care (eg. EPO, G-CSF or others) within 14 days before the initiate dose, and laboratory test should meet the following criteria: neutrophile count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, hemoglobin ≥90 g/L or ≥5.6 mmol/L, serum creatinine ≤1.5×ULN and creatinine clearance rate ≥30 mL/min, total bilirubin ≤1×ULN, AST and ALT ≤2.5×ULN (for patients with liver metastasis: ≤5×ULN)
9. Female or male patient of childbearing age must agree to take effective contraception for the duration of treatment plus six months post-treatment completion; female patient must have a negative serum pregnancy test within 7 days before enrollment and must not be lactating female.
10. Able to understand and provide an informed consent.

Exclusion Criteria:

1. Patients with large cell neuroendocrine lung carcinoma or combined small cell lung carcinoma.
2. Patients with history of immunotherapy-induced colitis or pneumonia, confirmed by clinical assessment and/or biopsy.
3. Patients with central Nervous System (CNS) metastasis meet any of the following criteria: a) Patient who have developed new or progressive brain metastasis following cranial radiation; b) Patients with the symptomatic Central Nervous System (CNS) metastasis who have used cortisol, radiotherapy, dehydration drugs, etc. to control symptoms in the past two weeks; c) Patients with carcinomatous meningitis; d) Patients with brain stem (midbrain, pons, medulla oblongata) or spinal cord metastasis.
4. Uncontrolled third lacunar effusion, not suitable for enrollment by investigator's assessment.
5. Previous malignancies in the past five years (except for basal cell carcinoma, squamous cell carcinoma, superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of cervical, or of others that have been radically resected and have not recurred).
6. Patients who have received any of the following treatments, a) Patients who have received prior topoisomerase I inhibitor treatment, including irinotecan or other investigational agents; b) Patients who have used any antibody-drug conjugates or molecular targeted preparation alone or in combination setting; c) Patients who have received more than one line of immunotherapy (immunotherapy in first-line as single or combination is permitted).
7. Concomitant use of strong CYP3A4 inducers within 2 weeks or strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 1 week of the first dose of the study drug.
8. Patients who have received any chemotherapy, biological therapy, endocrinotherapy, immunotherapy or investigational therapy within 4 weeks (5 half-lives of the agent, whichever is longer) of the first dose of the study drug, or local palliative radiotherapy or Chinese herbal medicine with anti-tumor indications within 2 weeks of the first dose of the study drug.
9. Any major surgery or severe trauma within 4 weeks of the first dose, not including biopsy.
10. Severe cardiovascular disease within 6 months prior to enrollment.
11. Severe pulmonary disease within 6 months prior to enrolment, such as interstitial pneumonia, pulmonary fibrosis, radiation induced pneumonitis requiring steroid therapy, and other moderate and severe lung diseases which affect lung function.
12. Uncontrolled active bleeding or known hemorrhagic constitution.
13. Any active infection, in the investigator's opinion, would increase the risk or have an influence on the result of the study, such as acute bacterial infection, tuberculosis, active hepatitis B/C, or HIV infection.
14. Known hypersensitivity to any of the components of irinotecan liposome injection, or other liposomal products.
15. Clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1.
16. History of explicit neurological or psychiatric disorders, including epilepsy or dementia.
17. Pregnant or lactating female.
18. Patient is not suitable for the study in the investigator's opinion.

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: irinotecan liposome injection; Patients will receive irinotecan liposome injection at 70 mg/m^2 intravenously, over 90 min on Days 1 of every 14-day cycle.	Drug: irinotecan liposome injection; Drug: irinotecan liposome injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the proportion of patients who achieved partial response or complete response according to RECIST V1.1 guidelines.	From date of first dose until the date of first documented progression, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	from date of the first dose to date of the first documented disease progression (PD) per RECIST v1.1 or death due to any cause, whichever occurs first.	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall survival (OS)	from date of the first dose to date of death from any cause	From date of first dose until the date of death from any cause , assessed up to 24 months
Proportion of Patients with Symptom Improvement	Patient-reported EORTC-QLQ symptom scales	date of the first dose to 30 days after permanent treatment termination
Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs) and laboratory abnormalities	Incidence of AE, SAE and laboratory abnormalities	date of the first dose to 30 days after permanent treatment termination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters-Cmax	Cmax of total, encapsuled and free irinotecan	Cycle 1（each cycle is 14 days）
PK parameters-AUC	AUClast, AUCinf of total, encapsuled and free irinotecan	Cycle 1（each cycle is 14 days）
PK parameters-others	tmax, tlast, t1/2 of total, encapsuled and free irinotecan	Cycle 1（each cycle is 14 days）

Collaborators and Investigators

• Sponsor: CSPC Ouyi Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yin Cheng, Professor, Jilin Provincial Tumor Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: HE072-CSP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No