Clinical trial NCT05572476: Lurbinectedin Combined With Durvalumab in Pre-treated Patients With Extensive Stage Small-cell Lung Cancer
Official title: Lurbinectedin Combined With Durvalumab in Pre-treated Patients With Extensive Stage Small-cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Platinum-Sensitive Lung Small Cell Carcinoma
Extensive-stage Small-cell Lung Cancer
Keywords: small cell lung cancer
platinum sensitive
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: PharmaMar
First posted: 2022-10-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized phase II study in which eligible patients will be randomized (2:1) according to two therapeutic strategies
Primary purpose: TREATMENT

Brief summary: Multicenter, prospective, open-labeled, 2-arm, randomized non-comparative (2:1) phase II trial assessing the efficacy of lurbinectedin in association with durvalumab

Detailed description: Multicenter, prospective, open-labeled, 2-arm, randomized non-comparative (2:1) phase II trial assessing the efficacy of lurbinectedin in association with durvalumab in pre-treated patients with platinum sensitive extensive stage small-cell lung cancer (SCLC) which failed one prior platinum-containing regimen.

Eligibility criteria: Inclusion Criteria:

1. Histology: confirmed diagnosis of extensive stage SCLC which failed one prior platinum-containing regimen,
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. Patients 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 ≤ 1,
7. Life expectancy \> 3 months,
8. Patients must have measurable disease as per RECIST v1.1.
9. Documented disease progression according to RECIST v1.1 before study entry,
10. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment for neoplastic disease and/or radiotherapy,
11. Adequate hematological, renal, metabolic and hepatic function
12. 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 ,
13. 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,
14. Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the NCI-CTCAE, version 5,
15. Body weight \>30kg
16. Voluntarily signed and dated written informed consent prior to any study specific procedure,
17. Patients with a social security in compliance with the French law.

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,
3. Active or prior documented inflammatory bowel disease,
4. Has an active autoimmune disease requiring systemic treatment within the past 2 years,
5. Has evidence of active non-infectious pneumonitis,
6. Has an active or ongoing infection requiring systemic therapy,
7. Currently active bacterial or fungus infection, HIV1, HIV2, hepatitis A or hepatitis B or hepatitis C infections,
8. Symptomatic untreated, or steroid-requiring, or progressing central nervous system malignancy 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,
13. Known hypersensitivity to any involved study drug or any of its formulation components,
14. Tumors not accessible for biopsy,
15. Active infection including tuberculosis,
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,
20. Presence of any external drainage,
21. Known myopathy,
22. Concomitant administration of any other antineoplastic therapy, other investigational agents, immunosuppressive therapies, Aprepitan or any other NK-1 antagonist,
23. Major surgical procedure within 28 days prior to the first dose of durvalumab.
24. History of allogenic organ transplantation,
25. History of leptomeningeal carcinomatosis,
26. QT interval corrected for heart rate using Fridericia's formula ≥470 ms

Primary outcomes:
measure: Assessment of the antitumor activity of lurbinectedin combined with durvalumab
timeFrame: 6 months
Secondary outcomes:
measure: 6-months objective response for experimental Arm
timeFrame: 6 months
measure: Best overall response for experimental Arm
timeFrame: Throughout the treatment period, an expected average of 6 months
measure: 1-year progression-free survival for experimental Arm
timeFrame: 1 year
measure: 2-year progression-free survival for experimental Arm
timeFrame: 2 years
measure: 1-year overall survival for experimental Arm
timeFrame: 1 year
measure: 2-years overall survival for experimental Arm
timeFrame: 2 years
measure: Safety profile for experimental Arm: Common Terminology Criteria for Adverse Events version 5
timeFrame: Throughout the treatment period, an expected average of 6 months
measure: Safety profile for standard Arm: Common Terminology Criteria for Adverse Events version 5
timeFrame: Throughout the treatment period, an expected average of 6 months
measure: Assessment of the antitumor activity of carboplatin combined with etoposide
timeFrame: 6 months
measure: 6-months objective response for standard Arm
timeFrame: 6 months
measure: Best overall response for standard Arm
timeFrame: Throughout the treatment period, an expected average of 6 months
measure: 1-year progression-free survival for standard Arm
timeFrame: 1 year
measure: 2-year progression-free survival for standard Arm
timeFrame: 2 years
measure: 1-year overall survival for standard Arm
timeFrame: 1 year
measure: 2-years overall survival for standard Arm
timeFrame: 2 years
measure: Tumor immune cells levels
timeFrame: before treatment onset, at cycle 2 days 1, cycle 3 day 1 and at progression (each cycle is 21 days)
measure: Blood cytokines levels
timeFrame: before treatment onset, at cycle 2 days 1, cycle 3 day 1 and at progression (each cycle is 21 days)
measure: Blood lymphocytes levels
timeFrame: before treatment onset, at cycle 2 days 1, cycle 3 day 1 and at progression (each cycle is 21 days)
measure: Blood kynurenine levels
timeFrame: before treatment onset, at cycle 2 days 1, cycle 3 day 1 and at progression (each cycle is 21 days)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
Study officials:
References: