platinum sensitive extensive stage small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: LURBINECTEDIN
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Lurbinectedin
Current Sponsor code: Lurbinectedin
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Institut Bergonié
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histology: confirmed diagnosis of extensive stage SCLC which failed one prior platinum-containing regimen (see inclusion criteria n°3), 2. Recurrent and platinum-sensitive SCLC: defined as those patients with SCLC recurrence at least 90 days from the last dose of platinum-based chemotherapy. Definition of platinum-sensitive disease is patient with at least 90 days of progression-free duration after finishing first-line platinum-based chemotherapy 3. Patiens must have received as first line a combo with platinum+ etoposide + PD_L1 inhibitor 4. Metastatic or unresectable locally advanced disease, not ammenable to curative therapy, 5. Age = 18 years, 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1, 7. Life expectancy > 3 months, 8. Patients must have measurable disease (lesion in previously irradiated field can be considered as measurable if progressive at inclusion according to RECIST v1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as =10 mm with spiral CT scan. 9. Documented disease progression according to RECIST v1.1 before study entry, 10. Patient must comply with the collection of tumor biopsies, 11. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment for neoplastic disease and/or radiotherapy, 12. Adequate hematological, renal, metabolic and hepatic function 13. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for three months after discontinuation of treatment for patients treated in experimental arm, and for seven months after discontinuation of treatment for patients treated in standard arm. Acceptable methods of contraception are described in protocol section 7.5.1, 14. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, concomitant endometrial carcinoma stage IA grade 1, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma, 15. Recovery to grade = 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade = 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5), 16. Body weight >30kg 17. Voluntarily signed and dated written informed consent prior to any study specific procedure, 18. Patients with a social security in compliance with the French law Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 41 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 41
Exclusion criteria
Exclusion criteria: 1. Previous treatment with lurbinectedin, 2. Current or prior use of immunosuppressive medication including any use of oral glucocorticoids, within 14 days before the first dose of durvalumab, with the exceptions of topical, intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses ( grade 2 NCI-CTCAE), HIV1, HIV2, hepatitis A or hepatitis B or hepatitis C infections, (For hepatitis B, this includes known positive tests for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR). For hepatitis C, this includes known positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR). 8. Symptomatic untreated, or steroid-requiring, or progressing central nervous system malignancy (CNS) is excluded. 9. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding, 10. Previous enrolment in the present study, 11. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons, 12. Has received a live vaccine within 30 days prior to the first dose of trial treatment, Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Note that patient should not receive live vaccine while receiving study drugs and up to 30 days after the last dose. For Covid-19 vaccines: only inactivated vaccines are allowed and a wash-out period of at least 14 days is recommended prior to the first study drug infusion. 13. Known hypersensitivity to any involved study drug or any of its formulation components, 14. Concomitant treatment with phenytoin and/or fosphenytoin 15. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings and TB testing as per local practice), 16. Person under judicial protection or deprived of liberty, 17. Concomitant use of strong inhibitors or inductors of cytochrome CYP3A4 taken within 21 days prior to the first dose of study drug, 18. Uncontrolled symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, clinically significant valvular heart disease, 19. Intermittent or continuous oxygen requirement. Patients with confirmed or suspected diagnosis of diffuse interstitial lung disease or pulmonary fibrosis, 20. Presence of any external drainage, 21. Known myopathy, 22. Concomitant administration of any other antineoplastic therapy, other investigati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antitumor activity of lurbinectedin in association with durvalumab in terms of 6-month progression-free rate (rate of patients with complete or partial responses or stable disease at week 24, as per RECIST v1.1 criteria) after blinded centralized radiological review, in pre-treated patients with platinum sensitive extensive stage small-cell lung cancer which failed one prior platinum-containing regimen.;Secondary Objective: •To evaluate the antitumor activity of lurbinectedin in association with durvalumab in terms of additional efficacy endpoints: o6-month objective response, best overall response, 1 and 2-year progression-free survival (PFS) (as per RECIST v1.1 criteria), o1 and 2-year overall survival (OS), •To evaluate the toxicity profile of lurbinectedin in association with durvalumab (NCI-CTCAE v5). •To evaluate the antitumor activity and the toxicity profile of the association Carboplatin + Etoposide (Arm B) (same endpoints as for the analysis of the association lurbinectedin + durvalumab [Arm A]). •To perform pharmacodynamics (PD) / mechanisms of action (MOA) biomarker analysis as well as analysis of predictive biomarkers (levels of immunologic biomarkers in blood / tissue) at baseline and different time points.;Primary end point(s): Efficacy of each intervention (experimental / standard) will be assessed, independently for each arm, in terms of 6-month progression-free rate (PFR), as per blinded central reviewer. PFR will be defined as the rate of patients with complete responses, partial response or stable disease, as per RECIST v1.1 criteria at week 24. ;Timepoint(s) of evaluation of this end point: 6 months after treatment onset | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): oAntitumor activity will be assessed in terms of additional efficacy endpoints, independently for each arm: oObjective response(ORR) defined as complete response, partial response or unconfirmed partial response. 6-month ORR will be reported independently for each arm. To be considered as confirmed, claimed responses will have to be confirmed 4 weeks later. Otherwise, responses will be considered as unconfirmed. oBest overall response defined as the best response across all time points as per RECIST v1.1. oGrowth modulation index, defined for each patient as the ratio of the PFS on the current treatment strategy to the PFS on the previous line of therapy (Von Hoff, 1998), in patients with documented progression at inclusion. oProgression-free survival (PFS) defined as the delay between the start date of treatment and the date of progression (as per RECIST v1.1) or death (from any cause), whichever occurs first. Median PFS, 1- and 2-year PFS rates will be reported. oOverall survival (OS) defined as the delay between the start date of treatment and the date of death (of any cause). Median OS, 1- and 2-year OS rates will be reported. oSafety. Events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) from the NCI v5.0. Both AE and SAE wille be coded according to the standardized medical terminology MedDRA. oTranslational study that aims to identify through a multi-parametric approach and rigourous bioinformatics and statistical analyses, predictive biomarkers of immunotherapy based on genetic, immunologival and metabolomics profiling of immune and tumor cells.;Timepoint(s) of evaluation of this end point: Objective response: 6 months after treatment onset Best overall response: throughout the treatment period, an expected average of 6 months Growth Modulation index: until progression under treatlent, an expected average of 6 months Progression-free survival : at 1 year and 2 years Overall survival: at 1 year and 2 | — |
Countries
France
Contacts
Public ContactRegulatory Affairs Management Desk
Institut Bergonié
Outcome results
None listed