Study Stopped
Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the GO41864 study.
A Study Evaluating The Safety, Tolerability, Pharmacokinetics, And Efficacy Of Venetoclax In Combination With Atezolizumab, Carboplatin, And Etoposide In Participants With Untreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC).
A Phase Ib Dose-Escalation and Dose-Expansion Study Evaluating The Safety, Tolerability, Pharmacokinetics, And Efficacy Of Venetoclax In Combination With Atezolizumab, Carboplatin, And Etoposide In Patients With Untreated Extensive-Stage Small Cell Lung Cancer.
2 other identifiers
interventional
2
4 countries
5
Brief Summary
A study consisting of a dose-escalation phase and a dose-expansion phase to evaluate the safety, tolerability, pharmacokinetics, and efficacy of venetoclax in combination with atezolizumab, carboplatin, and etoposide.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Sep 2020
Shorter than P25 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 5, 2020
CompletedFirst Posted
Study publicly available on registry
June 9, 2020
CompletedStudy Start
First participant enrolled
September 22, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 6, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 6, 2020
CompletedResults Posted
Study results publicly available
November 8, 2021
CompletedNovember 8, 2021
October 1, 2021
2 months
June 5, 2020
October 8, 2021
October 8, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants With Adverse Events (AEs)
The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Baseline up until 30 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 6.5 weeks).
Overall Response Rate (ORR)
The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Up to 24 months
Secondary Outcomes (9)
Duration of Response (DOR)
Up to 24 months
Progression Free Survival (PFS)
Up to 24 months
Overall Survival (OS) After Enrolment
Up to 49 months
Progression Free Survival (PFS) Rate at 6 Months
Up to 18 months
Overall Survival (OS) Rate at 1 Year
Up to 18 months
- +4 more secondary outcomes
Study Arms (8)
Dose Escalation (Arm A1) (Maintenance only)
EXPERIMENTALCohort A1: Participants with ES-SCLC who completed 4-6 cycles of carboplatin and etoposide first-line induction chemotherapy, with or without atezolizumab, were administered continuous maintenance therapy with Venetoclax (400mg) once daily (QD) from Day 1 to 21 and Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1.
Dose Escalation (Arm A2) (Maintenance only)
EXPERIMENTALCohort A2: Participants with ES-SCLC who completed 4-6 cycles of carboplatin and etoposide first-line induction chemotherapy, with or without atezolizumab, were to be administered continuous maintenance therapy with Venetoclax (800mg) once daily (QD) from Day 1 to 21 and Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1.
Dose Escalation (Arm A3) (Maintenance only)
EXPERIMENTALCohort A3: Participants with ES-SCLC who completed 4-6 cycles of carboplatin and etoposide first-line induction chemotherapy, with or without atezolizumab, were to be administered continuous maintenance therapy with Venetoclax (200mg) once daily (QD) from Day 1 to 21 and Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1. This cohort maybe explored if Dose-Limiting Toxicities (DLTs) are experienced and adverse events are thought to be potentially mitigated with a lower dose of venetoclax.
Dose Escalation (Arm B1) (Induction + Maintenance)
EXPERIMENTALCohort B1: Participants with ES-SCLC were to be administered non-continuous induction therapy with Venetoclax (200mg) once daily (QD) from Day 1 to 7, Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1, Carboplatin (5mg/mL/min) on Day 1 and Etoposide (100mg/m\^2) on Days 1-3. Participants who tolerated study treatment without excessive toxicity, and had not undergone disease progression were to be then proceeded to maintenance treatment with venetoclax plus atezolizumab. The venetoclax dose for the maintenance setting in Arm B will be the dose that has been cleared in the maintenance only arm (Arm A) of the study (maintenance RP2D, RP2D-M).
Dose Escalation (Arm B2) (Induction + Maintenance)
EXPERIMENTALCohort B2: Participants with ES-SCLC were to be administered non-continuous induction therapy with Venetoclax (400mg) once daily (QD) from Day 1 to 7, Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1, Carboplatin (5mg/mL/min) on Day 1 and Etoposide (100mg/m\^2) on Days 1-3. Participants who tolerated study treatment without excessive toxicity, and had not undergone disease progression were to be then proceeded to maintenance treatment with venetoclax plus atezolizumab. The venetoclax dose for the maintenance setting in Arm B will be the dose that has been cleared in the maintenance only arm (Arm A) of the study (maintenance RP2D, RP2D-M).
Dose Escalation (Arm B3) (Induction + Maintenance)
EXPERIMENTALCohort B3: Participants with ES-SCLC were to be administered non-continuous induction therapy with Venetoclax (800mg) once daily (QD) from Day 1 to 7, Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1, Carboplatin (5mg/mL/min) on Day 1 and Etoposide (100mg/m\^2) on Days 1-3. Participants who tolerated study treatment without excessive toxicity, and had not undergone disease progression were to be then proceeded to maintenance treatment with venetoclax plus atezolizumab. The venetoclax dose for the maintenance setting in Arm B will be the dose that has been cleared in the maintenance only arm (Arm A) of the study (maintenance RP2D, RP2D-M).
Dose Escalation (Arm B4) (Induction + Maintenance)
EXPERIMENTALCohort B4: Participants with ES-SCLC were to be administered non-continuous induction therapy with Venetoclax (800mg) once daily (QD) from Day 1 to 14, Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1, Carboplatin (5mg/mL/min) on Day 1 and Etoposide (100mg/m\^2) on Days 1-3. Participants who tolerated study treatment without excessive toxicity, and had not undergone disease progression were to be then proceeded to maintenance treatment with venetoclax plus atezolizumab. The venetoclax dose for the maintenance setting in Arm B will be the dose that has been cleared in the maintenance only arm (Arm A) of the study (maintenance RP2D, RP2D-M).
Dose Expansion
EXPERIMENTALIf the Recommended Phase II Dose (RP2D) for Venetoclax during induction is established, then the dose-expansion cohort would continue to test venetoclax in both induction and maintenance. Participants would be administered non-continuous induction therapy with Venetoclax (RP2D-I/induction RP2D), Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1, Carboplatin (5mg/mL/min) on Day 1 and Etoposide (100mg/m\^2) on Days 1-3 followed by continuous maintenance therapy with Venetoclax (RP2D-M) and Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1. If significant toxicity and DLTs in induction precluded identification of an RP2D for venetoclax in induction treatment, then the safety and efficacy of venetoclax would only be investigated in dose-expansion in the maintenance setting. Participants would be administered continuous maintenance therapy with Venetoclax (RP2D-M) and Atezolizumab (1200mg) every 3 weeks (Q3W) on Day 1.
Interventions
Venetoclax will be administered orally at escalating doses from 200mg to 800mg as 100mg tablets as per the dosing schedules described above.
Atezolizumab will be administered via intravenous (IV) infusion at a fixed dose of 1200mg as per the dosing schedules described above.
Carboplatin will be administered via IV infusion at a dose of 5mg/mL/min as per the dosing schedules described above.
Etoposide will be administered via IV infusion at a dose of 100mg/m\^2 as per the dosing schedules described above.
Eligibility Criteria
You may qualify if:
- Dose Escalation, Maintenance Arm A:
- Participants with ES-SCLC who have completed 4-6 cycles of carboplatin and etoposide induction chemotherapy, with or without atezolizumab, as their first-line therapy for extensive-stage disease and have responded (CR or PR) or have Stable Disease (SD) are eligible for the maintenance arm of the study.
- All side effects attributed to prior anti-cancer therapy must have resolved to Grade 1 or baseline.
- A maximum of 8 weeks (56 days) is allowed between last chemotherapy dose (Cycle 4, Day 3) given in induction and the start of maintenance therapy.
- Dose Escalation, Induction Arm B:
- Participants with no prior systemic treatment for ES-SCLC are eligible for this study.
- ANC \>= 1,500 cells/µL without granulocyte colony-stimulating factor support.
- Dose Expansion, Maintenance-Only:
- Participants with ES-SCLC who have completed 4 cycles of carboplatin and etoposide induction chemotherapy and at least 3 cycles of atezolizumab as their first-line therapy for extensive-stage disease and have responded (CR or PR) or have SD are eligible for the maintenance arm of the study.
- Dose Escalation (Arms A and B) and Dose Expansion:
- Ability to comply with the study protocol, in the investigator's judgement.
- ECOG performance status of 0 or 1.
- Participants must be able to swallow pills.
- Histologically or cytologically confirmed diagnosis of ES-SCLC per the Veterans Administration Lung Study Group (VALG) staging system.
- Participants who received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy or chemoradiotherapy cycle prior to diagnosis of ES-SCLC.
- +9 more criteria
You may not qualify if:
- Use of non-protocol-specified anti-cancer therapies or other combination partners with carboplatin/etoposide during induction.
- Symptomatic or actively progressing CNS metastases.
- Pregnant or breastfeeding, or intending to become pregnant during the study.
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>= 1 week prior to enrollment.
- Leptomeningeal disease.
- Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once a month or more frequently).
- Uncontrolled or symptomatic hypercalcemia.
- History of malignancy other than SCLC within 5 years prior to enrollment.
- History of autoimmune disease.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- Positive HIV infection.
- Active Hepatitis B and C infection (HBV/HCV).
- Active Tuberculosis infection.
- Known infection with human T-cell leukemia virus 1.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Emory University
Atlanta, Georgia, 30322, United States
Rigshospitalet; Onkologisk Klinik
København Ø, 2100, Denmark
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat, Barcelona, 08908, Spain
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, 28050, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated by the Sponsor. Only 2 participants were enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 5, 2020
First Posted
June 9, 2020
Study Start
September 22, 2020
Primary Completion
November 6, 2020
Study Completion
November 6, 2020
Last Updated
November 8, 2021
Results First Posted
November 8, 2021
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).