Small Cell Lung CancerPhase 1NCT04422210
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 1 study testing Venetoclax, Atezolizumab and Carboplatin in people with Small Cell Lung Cancer, run by Hoffmann-La Roche at 5 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- Venetoclax, Atezolizumab and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 22 Sep 2020to 6 Nov 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Participants with a history of treated CNS metastases that are currently asymptomatic.
- Measurable disease, as defined by RECIST v1.1. Baseline measurements and evaluation of all sites of disease must be obtained =<4 weeks prior to enrollment.
- Eligible to receive a carboplatin-based chemotherapy regimen.
- Adequate hematologic and end-organ function.
- Participants must submit a pre-treatment tumor tissue sample.
- Participants must submit a blood sample for exploratory biomarker research before treatment, on-study, and following progression of disease.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use non-hormonal contraceptive methods and refrain from donating eggs.
- Women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm.
Who cannot join
- 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).
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- 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.
- Significant cardiovascular disease.
- Major surgical procedure within 28 days prior to enrollment or anticipation of need for major surgical procedure during the course of the study.
- Prior allogenic bone marrow transplantation or solid organ transplant.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications.
- Illnesses or conditions that interfere with their capacity to understand, follow, and/or comply with study procedures.
- Treatment with investigational therapy with therapeutic intent within 28 days prior to enrollment.
- Administration of a live, attenuated vaccine within 4 weeks before enrollment or anticipation that such a live attenuated vaccine will be required during the study.
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
- Treatment with systemic immunosuppressive medications within 1 week prior to enrollment.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
- History of allergic reactions to carboplatin or etoposide or to any of its excipients (etoposide).
- Known hypersensitivity to venetoclax or to any of its excipients.
- Administration of Steroid therapy for anti-neoplastic intent, strong or moderate CYP3A inhibitors or strong or moderate CYP3A inducers within 7 days prior to the first dose of study drug.
- Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade-containing Seville oranges), or starfruit (carambola) within 3 days prior to the first dose of study drug.
- Malabsorption syndrome or other condition that would interfere with enteral absorption.
- Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgement.
- Inability or unwillingness to swallow a large number of tablets.
- History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Spain2 sites
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'Hospitalet de Llobregat, Barcelona, 08908
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, 28050
South Korea1 site
Severance Hospital, Yonsei University Health System
Seoul, 03722
About this study
Official title: 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.
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.
- Conditions
- Small Cell Lung Cancer
- Being tested
- Venetoclax, Atezolizumab, Carboplatin, Etoposide
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Venetoclax will be administered orally at escalating doses from 200mg to 800mg as 100mg tablets as per the dosing schedules described above.
AtezolizumabDrug
Atezolizumab will be administered via intravenous (IV) infusion at a fixed dose of 1200mg as per the dosing schedules described above.
CarboplatinDrug
Carboplatin will be administered via IV infusion at a dose of 5mg/mL/min as per the dosing schedules described above.
EtoposideDrug
Etoposide will be administered via IV infusion at a dose of 100mg/m^2 as per the dosing schedules described above.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Arm A1) (Maintenance only) | Experimental | Cohort 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. Receives: Drug: Venetoclax; Drug: Atezolizumab |
| Dose Escalation (Arm A2) (Maintenance only) | Experimental | Cohort 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. Receives: Drug: Venetoclax; Drug: Atezolizumab |
| Dose Escalation (Arm A3) (Maintenance only) | Experimental | Cohort 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. Receives: Drug: Venetoclax; Drug: Atezolizumab |
| Dose Escalation (Arm B1) (Induction + Maintenance) | Experimental | Cohort 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). Receives: Drug: Venetoclax; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
| Dose Escalation (Arm B2) (Induction + Maintenance) | Experimental | Cohort 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). Receives: Drug: Venetoclax; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
| Dose Escalation (Arm B3) (Induction + Maintenance) | Experimental | Cohort 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). Receives: Drug: Venetoclax; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
| Dose Escalation (Arm B4) (Induction + Maintenance) | Experimental | Cohort 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). Receives: Drug: Venetoclax; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
| Dose Expansion | Experimental | If 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. Receives: Drug: Venetoclax; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 24 months
Secondary outcomes (9)
Duration of Response (DOR)
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.
Measured: Up to 24 months
Progression Free Survival (PFS)
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.
Measured: Up to 24 months
Overall Survival (OS) After Enrolment
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.
Measured: Up to 49 months
Progression Free Survival (PFS) Rate at 6 Months
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.
Measured: Up to 18 months
Overall Survival (OS) Rate at 1 Year
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.
Measured: Up to 18 months
Plasma Concentrations (ng/mL) of Venetoclax at Specified Timepoints
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.
Measured: Up to 24 months
Serum Concentrations (ng/mL) of Atezolizumab at Specified Timepoints
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.
Measured: Up to 24 months
Plasma Concentrations (ng/mL) of Carboplatin at Specified Timepoints
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.
Measured: Up to 24 months
Plasma Concentrations (ng/mL) of Etoposide at Specified Timepoints
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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start22 Sep 2020
- Primary completion6 Nov 2020
- Study completion6 Nov 2020
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04422210
- Sponsor's protocol ID
- GO41864
- Other IDs
- 2019-004487-22, 2019
- Status last verified
- Oct 2021
- First submitted
- 5 Jun 2020
- Last updated
- 8 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04422210
- Acronym / sponsor ID
- GO41864
- Conditions
- Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 6 Nov 2020 (actual)
- Study completion
- 6 Nov 2020 (actual)
- First posted
- 9 Jun 2020 (actual)
- Results
- Posted 8 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (Arm A1) (Maintenance only) | Experimental | Drug: Venetoclax, Drug: AtezolizumabCohort 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) | Experimental | Drug: Venetoclax, Drug: AtezolizumabCohort 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) | Experimental | Drug: Venetoclax, Drug: AtezolizumabCohort 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) | Experimental | Drug: Venetoclax, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideCohort 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) | Experimental | Drug: Venetoclax, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideCohort 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) | Experimental | Drug: Venetoclax, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideCohort 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) | Experimental | Drug: Venetoclax, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideCohort 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 | Experimental | Drug: Venetoclax, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideIf 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
- 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.
Key exclusion criteria (34 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxVenetoclax will be administered orally at escalating doses from 200mg to 800mg as 100mg tablets as per the dosing schedules described above. | Drug | Dose Escalation (Arm A1) (Maintenance only), Dose Escalation (Arm A2) (Maintenance only), Dose Escalation (Arm A3) (Maintenance only), Dose Escalation (Arm B1) (Induction + Maintenance), Dose Escalation (Arm B2) (Induction + Maintenance), Dose Escalation (Arm B3) (Induction + Maintenance), Dose Escalation (Arm B4) (Induction + Maintenance), Dose Expansion |
| AtezolizumabAtezolizumab will be administered via intravenous (IV) infusion at a fixed dose of 1200mg as per the dosing schedules described above. | Drug | Dose Escalation (Arm A1) (Maintenance only), Dose Escalation (Arm A2) (Maintenance only), Dose Escalation (Arm A3) (Maintenance only), Dose Escalation (Arm B1) (Induction + Maintenance), Dose Escalation (Arm B2) (Induction + Maintenance), Dose Escalation (Arm B3) (Induction + Maintenance), Dose Escalation (Arm B4) (Induction + Maintenance), Dose Expansion |
| CarboplatinCarboplatin will be administered via IV infusion at a dose of 5mg/mL/min as per the dosing schedules described above. | Drug | Dose Escalation (Arm B1) (Induction + Maintenance), Dose Escalation (Arm B2) (Induction + Maintenance), Dose Escalation (Arm B3) (Induction + Maintenance), Dose Escalation (Arm B4) (Induction + Maintenance), Dose Expansion |
| EtoposideEtoposide will be administered via IV infusion at a dose of 100mg/m^2 as per the dosing schedules described above. | Drug | Dose Escalation (Arm B1) (Induction + Maintenance), Dose Escalation (Arm B2) (Induction + Maintenance), Dose Escalation (Arm B3) (Induction + Maintenance), Dose Escalation (Arm B4) (Induction + Maintenance), Dose Expansion |
Primary outcome
Number of Participants With Adverse Events (AEs)
Time frame: 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).
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.
Overall Response Rate (ORR)
Time frame: Up to 24 months
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.
9 secondary outcomes
Duration of Response (DOR)
Time frame: Up to 24 months
Progression Free Survival (PFS)
Time frame: Up to 24 months
Overall Survival (OS) After Enrolment
Time frame: Up to 49 months
Progression Free Survival (PFS) Rate at 6 Months
Time frame: Up to 18 months
Overall Survival (OS) Rate at 1 Year
Time frame: Up to 18 months
Plasma Concentrations (ng/mL) of Venetoclax at Specified Timepoints
Time frame: Up to 24 months
Serum Concentrations (ng/mL) of Atezolizumab at Specified Timepoints
Time frame: Up to 24 months
Plasma Concentrations (ng/mL) of Carboplatin at Specified Timepoints
Time frame: Up to 24 months
Plasma Concentrations (ng/mL) of Etoposide at Specified Timepoints
Time frame: Up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Venetoclax, Atezolizumab and Carboplatin in people with Small Cell Lung Cancer, run by Hoffmann-La Roche at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Spain, United States, Denmark, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) (time frame: 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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2021.