Clinical trial NCT05142696: A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab
Official title: A Phase Ib/II Dose Finding Study Assessing Safety and Efficacy of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) in Combination With Carboplatin, Etoposide, and Atezolizumab in Induction and With Atezolizumab in Maintenance Phase
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Extensive Stage Small Cell Lung Cancer
Keywords: Extensive Stage Small Cell Lung Cancer
ES-SCLC
Radioligand therapy
RLT
[177Lu]Lu-DOTA-TATE
Lutathera
Lutetium (177Lu) oxodotreotide
Lutetium Lu 177 dotatate
atezolizumab
carboplatin
etoposide
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-12-02
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study aims to establish a safe and well tolerated dose of \[177Lu\]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in this setting and to assess preliminary efficacy of this combination treatment versus the combination of carboplatin, etoposide, and atezolizumab.The study will be essential to assess a new potential therapeutic option in participants with this aggressive cancer type.

Detailed description: The study for each participant consists of a Screening period, a Treatment period that includes an Induction treatment period and a Maintenance treatment period, and a Follow-up period.

The study will consist of a Phase Ib dose escalation with concurrent backfill part and a randomised controlled Phase II part.

During the screening period of up to 28 days before starting SCLC treatment, each participant will be assessed for somatostatin receptor (SSTR) expression by \[68Ga\]Ga-DOTA-TATE imaging PET/scan.

The dose escalation part in this study will be guided by the dose limiting toxicity (DLT) rate observed during the DLT period. To achieve a more robust dataset and to aid dose decisions, additional participants may be backfilled in each dose level.

Upon dedclaring RD, a 1:1 randomised Phase II with approximately 140 participants with newly diagnosed ES-SCLC will be enrolled and receive either \[177Lu\]Lu-DOTA-TATE at the RD in combination with carboplatin, etoposide and atezolizumab (experimental arm) or carboplatin, etoposide and atezolizumab alone (control arm).

Eligibility criteria: Key Inclusion Criteria:

* Participant is \>= 18 years on the day of signing informed consent form
* Histologically or cytologically confirmed ES-SCLC
* Presence of measurable disease (at least one target lesion) according to RECIST v1.1 assessed by conventional computed tomography (CT) scan
* No prior systemic treatment for ES-SCLC (except the first cycle of chemotherapy with or without atezolizumab of the induction period
* ECOG status =\< 1
* Provision of tumor tissue to support exploratory biomarker analysis
* Life expectancy of \>= 6 months

Key Exclusion Criteria:

* Participant has received prior therapy with an antibody or drug against immune checkpoint pathways
* Active autoimmune diseases or history of autoimmune diseases that may relapse
* Severe chronic or active infections (including active tuberculosis, HBV, or HCV infection) requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks before Cycle 1 Day 1
* Any major surgical procedure requiring general anesthesia =\< 28 days before Cycle 1 Day 1
* History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for participants participating in the study
* Known hypersensitivity to the active substances or any of the excipients of the study drugs
* Concurrent participation in another therapeutic clinical study

Primary outcomes:
measure: Phase 1b: Frequency of dose limiting toxicities (DLTs), Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to treatment discontinuation
timeFrame: Within the first six weeks of [177Lu]Lu-DOTA-TATE treatment]
measure: Phase ll: Overall survival (OS)
timeFrame: In the phase II part: From date of randomization until date of death from any cause, assessed up to 3 years (estimated final Overall Survival (OS) analysis)
Secondary outcomes:
measure: Phase lb: Objective Response Rate (ORR) based on Investigator assessment
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)
measure: Phase lb: Duration of Response (DOR)
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)
measure: Phase lb: Progression Free Survival (PFS) based on Investigator assessment
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final OS analysis)
measure: Phase lb: Overall Survival (OS)
timeFrame: From date of randomization until date of death from any cause, assessed up to 3 years (estimated final Overall Survival (OS) analysis)
measure: Phase lb: Time activity curves (TACs)
timeFrame: Week 7 Day 3
measure: Phase lb: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3
measure: Phase lb: Concentration of [177Lu]Lu-DOTA-TATE in blood over time
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Phase lb: Quantification of [177Lu]Lu-DOTA-TATE excreted from the body in urine
timeFrame: Week 7 Day 3 with urine collection from the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging (1-3 hours after [177Lu]Lu-DOTA-TATE infusion)
measure: Phase ll: Progression free survival (PFS) by investigator assessment
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final OS analysis)
measure: Phase ll: Objective Response Rate (ORR) by investigator assessment
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)
measure: Phase ll: Duration of Response (DOR) by investigator assessment
timeFrame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 3 years (estimated final Overall Survival (OS) analysis)
measure: Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATE
timeFrame: Week 7 Day 3 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 7 Day 4 (24 hours post-dose), Week 7 Day 5 (48 hours post-dose), Week 8 Day 3 (168 hours post-dose)
measure: Preliminary anti-tumor activity of [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in newly diagnosed participants with ES-SCLC
timeFrame: From date of randomisation until date of progression or date of death from any cause, whichever comes first, assessed for up to 3 years (estimated final OS analysis)
measure: Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs) within 48 hours after [68Ga]Ga-DOTA-TATE administration
timeFrame: up to 48 hours following the start of [68Ga]Ga-DOTA-TATE administration]
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Lombardi Cancer Center
state: District of Columbia
city: Athens
country: United States
facility: University Cancer and Blood Center LLC
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Edison
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals Of Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Guildford
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: