Clinical Trial of Lurbinectedin as Single-agent or in Combination with Irinotecan Versus Topotecan or Irinotecan in Patients with Relapsed Small-cell Lung Cancer

JRCT ID: jRCT2071230123

Registered date:13/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed Small Cell Lung Cancer
• Date of first enrollment: 08/05/2024
• Target sample size: 35
• Countries of recruitment: Australia,Japan,South Korea,Japan,Taiwan,Japan,Austria,Japan,Belgium,Japan,Bulgaria,Japan,Switzerland,Japan,Germany,Japan,Denmark,Japan,Spain,Japan,France,Japan,Georgia,Japan,UK,Japan,Hungary,Japan,Italy,Japan,Israel,Japan,Poland,Japan,Romania,Japan,Turkey,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,US,Japan
• Study type: Interventional

Intervention(s)

SCLC patients who failed one prior platinum-containing line will be enrolled and assigned to each treatment arm: two experimental arms consisting of lurbinectedin as single agent (Group A) or the combination of lurbinectedin with irinotecan (Group B) versus Investigator's Choice (topotecan or irinotecan) as control arm (Group C). Central randomization will be implemented; patients will be assigned to each treatment arm at a 1:1:1 ratio.
Patients in Japan who are randomized to Group C will only receive topotecan i.v.
- Experimental arm (Lurbinectedin) (Group A):
Patients in Japan will receive lurbinectedin 3.2 mg/m2 i.v. on Day 1 q3wk (every three weeks), with granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis.
- Experimental arm (Lurbinectedin plus Irinotecan) (GroupB):
Patients will receive irinotecan 75 mg/m2 i.v. on Day 1 q3wk followed by lurbinectedin 2.0 mg/m2 i.v. on Day 1 q3wk, with G-CSF.
On Day 8 of each cycle, irinotecan alone will be administered at the same dose and schedule as Day 1 (unless toxicities require dose omission).
- Control arm (Group C):
Topotecan:
Topotecan i.v.: Topotecan 1.0 mg/m2 daily on Days 1-5 q3wk. Topotecan i.v. will be administered according to the local label in Japan.

Outcome(s)

• Primary Outcome: Overall survival (OS) will be calculated from the date of randomization to the date of death or last contact (in this case, survival will be censored on that date).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Voluntary written informed consent of the patient obtained before any study-specific procedure.
2. Age>=18 years.
3. Histologically or cytologically confirmed diagnosis of SCLC.
4. One prior line of platinum-containing chemotherapy with/without anti-PD-1 or anti-PD-L1 (Note: at least 70% of patients included in the study have to be pretreated with anti-PD-1 or anti-PD-L1).
5. Chemotherapy-free interval (CTFI, time from the last dose of first-line platinum-containing chemotherapy to the occurrence of progressive disease) >= 30 days (independent of the immunotherapy maintenance, if applicable).
6. Patients with history of Central Nervous System (CNS) metastases can participate provided they are pretreated and radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeated imaging (note: repeated imaging should be performed during study screening), asymptomatic, and without requirement of steroid treatment for at least 7 days before the first dose of study treatment.
7. Eastern Cooperative Oncology Group (ECOG) PS <= 2.
8. Adequate hematological, renal, metabolic and hepatic function:
a) Hemoglobin >= 9.0 g/dL [patients may have received prior red blood cell (RBC) transfusion, if clinically indicated]; absolute neutrophil count (ANC) >= 2.0 x 10^9/L, and platelet count >= 100 x 10^9/L.
b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3.0 x upper limit of normal (ULN).
c) Total bilirubin <= 1.5 x ULN or direct bilirubin <= ULN.
d) Albumin >= 3.0 g/dL.
e) Calculated creatinine clearance (CrCL) >= 30 mL/min (using Cockcroft and Gault's formula).
9. At least three weeks since last prior antineoplastic treatment and recovery to grade <= 1 from any adverse event (AE) related to previous anticancer treatment (excluding sensory neuropathy, anemia, asthenia and alopecia, all grade <= 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.
10. Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.
11. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to seven months after treatment discontinuation. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.

Exclude criteria

1. Platinum-naive patients or patients pretreated with more than one prior chemotherapy regimen (including patients re-challenged with same initial regimen).
2. Prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
3. Active or untreated CNS metastases and/or carcinomatous meningitis.
4. Patients with limited-stage disease who are candidates for local or regional therapy, including PCI, thoracic RT or both, must have been offered that option and completed treatment or refused it prior to randomization.
5. Concomitant diseases/conditions:
a) History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
b) Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
c) Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
d) Known Gilbert's disease.
e) Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages.
f) Ongoing, treatment-requiring, non-neoplastic chronic liver disease of any origin. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR. Subjects taking hepatitis related antiviral therapy within six months prior to the first dose of study drugs will also be excluded.
g) Intermittent or continuous oxygen requirement within two weeks prior to randomization. Patients with confirmed or suspected diagnosis of diffuse interstitial lung disease or pulmonary fibrosis.
h) Patients with a second invasive malignancy treated with chemotherapy and/or RT. Patients with a previous malignancy that was completely resected with curative intention three or more years prior to randomization, except treated in situ carcinoma of the cervix, basal or squamous cell skin carcinoma, and in situ transitional cell bladder carcinoma and who has been continuously in remission since then will be permitted.
i) Limitation of the patient's ability to comply with the treatment or to follow the protocol.
j) Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.
k) Known human immunodeficiency virus (HIV) infection.
l) Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.
m) Evident symptomatic pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
n) Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study (e.g.; COVID-19 disease).
6) RT in more than 35% of the bone marrow.
7) History of previous bone marrow and/or stem cell transplantation and allogenic transplant.
8) Patient has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of inactivated vaccines is allowed.
9) Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
10) History of allergy or hypersensitivity to any of the study drugs or any of their excipients.
11) Women who are pregnant or breast feeding and fertile patients (men and women) who are not able to use a highly effective method of contraception.

Related Information

• Primary Sponsor: Kobayashi Takeshi
• Secondary ID(s): 2021-004471-13,NCT05153239