Clinical trial NCT04774380: Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer
Official title: A Phase IIIb, Single-arm, Multi-center, International Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer (LUMINANCE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Extensive-stage Small Cell Lung Cancer
Keywords: Chemotherapy
Aggressive malignancy
Programmed cell death ligand-1
Platinum-based chemotherapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-03-01
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Study to determine the safety and tolerability profile of durvalumab with platinum (cisplatin or carboplatin) plus etoposide (EP) as first-line treatment in participants with extensive-stage small-cell lung cancer.

Detailed description: The study will be conducted in North America, Europe and Turkey.

In this single arm study participants will be treated with with durvalumab alone and concurrently with platinum-based chemotherapy and etoposide during the study period until radiological disease progression, unless there is clinical progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met, as per investigator assessment.

Eligibility criteria: Inclusion Criteria:

* Histologically- or cytologically-documented ES-SCLC (stage IV \[T any, N any, M1 a/b\], or with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan (Brain metastases; must be asymptomatic or treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment)
* Participants must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide
* World Health Organization/ Eastern Cooperative Oncology Group performance status of 0 to 2 at enrollment Baseline computed tomography/ magnetic resonance imaging results of the brain, chest and abdomen (including liver and adrenal glands) within 28 days prior to the treatment initiation
* No prior exposure to immune-mediated therapy including, but not limited to, other anti- CTLA-4, anti-Programmed cell death-1 (PD-1), anti- Programmed cell death ligand-1 (PD-L1), and anti-PD-L2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines
* Adequate organ and marrow function
* Body weight \> 30 kg
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants

Exclusion Criteria:

* History of allogeneic organ transplantation
* Active or prior documented autoimmune or inflammatory disorders, systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent
* History of another primary malignancy except for:

  * Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of Investigational medicinal product (IMP) and of low potential risk for recurrence
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  * Adequately treated carcinoma in situ without evidence of disease
* History of leptomeningeal carcinomatosis and active primary immunodeficiency
* Active infection including tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus
* Any unresolved toxicity Common Terminology Criteria for Adverse Events Grade ≥ 2 from previous anticancer therapy
* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
* Received prior systemic therapy for ES-SCLC
* Medical contraindication to platinum (cisplatin or carboplatin)-etoposide-based chemotherapy
* Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable
* Planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care is allowed but must be completed before first dose of the study medication
* Receipt of live attenuated vaccine within 30 days prior to the first dose of in IMP
* Major surgical procedure within 28 days prior to the first dose of IMP
* Participants who have received prior immunotherapy agents including anti-PD-1 or anti PD-L1
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
* Participation in another clinical study with an investigational product administered in the last 4 weeks
* Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 180 days after the last dose of etoposide

Primary outcomes:
measure: Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs)
timeFrame: From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
measure: Number of Participants With Incidence of Immune Mediated Adverse Events (imAEs)
timeFrame: From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From first dose of study treatment until disease progression or death, up to 2.5 years.
measure: Percentage of Participants Alive and Progression-free at 12 Months From First Date of Treatment (PFS12)
timeFrame: From first date of study treatment until 12 months.
measure: Objective Response Rate (ORR)
timeFrame: From screening until disease progression or the last evaluable assessment in the absence of progression, up to 2.5 years.
measure: Duration of Response (DoR)
timeFrame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.
measure: Percentage of Participants Remaining in Response, 12 Months After First Documented Objective Response (DoR12)
timeFrame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.
measure: Overall Survival (OS)
timeFrame: From first dose of study treatment to death, up to 2.5 years.
measure: Percentage of Participants Alive at 12 Months From First Date of Treatment (OS12)
timeFrame: From first dose of study treatment till 12 months.
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.
measure: Number of Participants With Adverse Events of Special Interests
timeFrame: From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.
Other outcomes:
Locations:
city: Panagyurishte
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Burgas
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Adapazari
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Pamukkale
country: Turkey
facility: Research Site
Study officials:
References: