Lurbinectedin Combined With Durvalumab in Pre-treated Patients With Extensive Stage Small-cell Lung Cancer

NCT05572476 | Withdrawn Phase 2 DMC

• 2 other identifiers: IB 2022-012022-001114-19
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Conditions

Small Cell Lung Cancer; Platinum-Sensitive Lung Small Cell Carcinoma; Extensive-stage Small-cell Lung Cancer

Keywords

small cell lung cancer; platinum sensitive

Outcome Measures

Primary Outcomes (1)

• Assessment of the antitumor activity of lurbinectedin combined with durvalumab

  Antitumor activity will be assessed in terms of of 6-month progression-free rate (rate of complete or partial responses or stable disease more than 24 weeks, as per RECIST v1.1 criteria) after blinded centralized radiological review

  6 months

Secondary Outcomes (19)

• 6-months objective response for experimental Arm

  6 months

• Best overall response for experimental Arm

  Throughout the treatment period, an expected average of 6 months

• 1-year progression-free survival for experimental Arm

  1 year

• 2-year progression-free survival for experimental Arm

  2 years

• 1-year overall survival for experimental Arm

  1 year

Study Arms (2)

Experimental Arm A: treatment by lurbinectedin and durvalumab

EXPERIMENTAL

Patients with with platinum sensitive extensive stage small-cell lung cancer (SCLC) which failed one prior platinum-containing regimen will be treated by the association of lurbinectedin and durvalumab

Drug: Association of lurbinectedin and durvalumab

Standard Arm B: treatment by carboplatin and etoposide

OTHER

Patients with with platinum sensitive extensive stage small-cell lung cancer (SCLC) which failed one prior platinum-containing regimen will be treated by the association of carboplatin and etoposide

Drug: Association of carboplatin and etoposide

Interventions

Association of lurbinectedin and durvalumab DRUG

A treatment cycles consists of 3 weeks (i.e. 21 days). Lurbinectedin will be administered by intravenous infusion on Day 1 every 3 weeks. Durvalumab will be administered by intravenous infusion on Day 1 every 3 weeks.

Experimental Arm A: treatment by lurbinectedin and durvalumab

Association of carboplatin and etoposide DRUG

Treatment will be administered on a 21-days cycle basis up to a maximum of 6 cycles. Carboplatin will be administered by intravenous infusion on Day 1 every 3 weeks. Etoposide will be administered by intravenous infusion on Day 1-3 every 3 weeks

Standard Arm B: treatment by carboplatin and etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histology: confirmed diagnosis of extensive stage SCLC which failed one prior platinum-containing regimen,
• 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
• Patients must have received as first line a combo with platinum+ etoposide + PD\_L1 inhibitor
• Metastatic or unresectable locally advanced disease, not ammenable to curative therapy,
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group ≤ 1,
• Life expectancy \> 3 months,
• Patients must have measurable disease as per RECIST v1.1.
• Documented disease progression according to RECIST v1.1 before study entry,
• At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment for neoplastic disease and/or radiotherapy,
• Adequate hematological, renal, metabolic and hepatic function
• 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 ,
• 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,
• 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,
• Body weight \>30kg

You may not qualify if:

• Previous treatment with lurbinectedin,
• Current or prior use of immunosuppressive medication including any use of oral glucocorticoids, within 14 days before the first dose of durvalumab,
• Active or prior documented inflammatory bowel disease,
• Has an active autoimmune disease requiring systemic treatment within the past 2 years,
• Has evidence of active non-infectious pneumonitis,
• Has an active or ongoing infection requiring systemic therapy,
• Currently active bacterial or fungus infection, HIV1, HIV2, hepatitis A or hepatitis B or hepatitis C infections,
• Symptomatic untreated, or steroid-requiring, or progressing central nervous system malignancy is excluded.
• 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,
• Previous enrolment in the present study,
• Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
• Has received a live vaccine within 30 days prior to the first dose of trial treatment,
• Known hypersensitivity to any involved study drug or any of its formulation components,
• Tumors not accessible for biopsy,
• Active infection including tuberculosis,

Sponsors & Collaborators

• Institut Bergonié: lead
• AstraZeneca: collaborator
• PharmaMar: collaborator

Study Sites (1)

Institut Bergonié

Bordeaux, 33076, France

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized phase II study in which eligible patients will be randomized (2:1) according to two therapeutic strategies

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 7, 2022
• Study Start: October 1, 2023
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: June 5, 2024

Record last verified: 2024-06

Locations

FR (1)