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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Level 1 (DL1) 		Dose Level 1 (DL1): [177Lu]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then [177Lu]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.
  • Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: - 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 - 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other names:
    • Lutathera
    • Lutetium (177Lu) oxodotreotide
    • Lutetium Lu 177 dotatate
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Experimental
Dose Level 2a (DL2a) 		Dose Level 2a (DL2a): [177Lu]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then [177Lu]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.
  • Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: - 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 - 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other names:
    • Lutathera
    • Lutetium (177Lu) oxodotreotide
    • Lutetium Lu 177 dotatate
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Experimental
Dose Level 2b (DL2b) 		Dose Level 2b (DL2b): [177Lu]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then [177Lu]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.
  • Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: - 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 - 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other names:
    • Lutathera
    • Lutetium (177Lu) oxodotreotide
    • Lutetium Lu 177 dotatate
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Experimental
Dose Level 3a (DL3a) 		Dose Level 3a (DL3a): [177Lu]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then [177Lu]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.
  • Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: - 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 - 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other names:
    • Lutathera
    • Lutetium (177Lu) oxodotreotide
    • Lutetium Lu 177 dotatate
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Experimental
Dose Level 3b (DL3b) 		Dose Level 3b (DL3b): [177Lu]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then [177Lu]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
  • Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: - 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 - 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other names:
    • Lutathera
    • Lutetium (177Lu) oxodotreotide
    • Lutetium Lu 177 dotatate
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Experimental
Dose Level 4 (DL4) 		Dose Level 4 (DL4): [177Lu]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then [177Lu]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.
  • Drug: [177Lu]Lu-DOTA-TATE
    Solution for infusion of [177Lu]Lu-DOTA-TATE will be administered as follows: - 2 administrations during the induction period on either Day 3, 4 or 5 of Week 1 and on Week 7 Day 3 - 1 to 4 administrations during the maintenance period on Week 13 Day 1, Week 16 Day 1, Week 19 Day 1 and Week 22 Day 1, depending on the dose assessed
    Other names:
    • Lutathera
    • Lutetium (177Lu) oxodotreotide
    • Lutetium Lu 177 dotatate
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Experimental
Phase II Experimental arm 		[177Lu]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
Other
Phase II Control arm 		Carboplatin, etoposide and atezolizumab alone (control arm)
  • Drug: Atezolizumab
    Atezolizumab 1200 mg on Day 1 from Cycle 2 every 3 weeks in induction and maintenance period
  • Drug: [68Ga]Ga-DOTA-TATE
    2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi)
  • Other: Carboplatin
    Four cycles of carboplatin AUC 5 on Day 1 every 3 weeks (Weeks 1, 4, 7 and 10) in induction period
  • Other: Etoposide
    Four cycles of etoposide 100 mg/m2 on Day 1-3, every 3 weeks (Weeks 1, 4, 7 and 10) in induction period

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40536
Contact:
859-218-5151

More Details

NCT ID
NCT05142696
Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.