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Small-cell Lung CancerPhase 2NCT04610684

Chemotherapy and Atezolizumab for Patients With Extensive Stage Small Cell Lung Cancer (SCLC) With Untreated, Asymptomatic Brain Metastases

A Phase 2 study testing Carboplatin, Etoposide and Atezolizumab in people with Small-cell Lung Cancer and Brain Metastases, run by Jeffrey Clarke at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a single arm, multicenter phase II trial for 60 patients with untreated extensive stage (ES) small cell lung cancer (SCLC) with asymptomatic brain metastases. Subjects will receive 4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) 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, Brain Metastases
What is being tested?
Carboplatin, Etoposide and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
6 sitesUnited States
Study dates
5 Jan 2021to 20 Sep 2022
Phase
Phase 2
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

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years with ability and willingness to provide informed consent.
  • ECOG Performance Status of 0-2.
  • Histological confirmation of Small Cell Lung Cancer- Extensive Stage (SCLC) per Veterans Administration Lung Study Group (VALG).
  • At least one untreated asymptomatic brain metastasis that is measurable by RECIST 1.1 that has not been previously irradiated.
  • No prior treatment for metastatic disease. EXCEPTION: A single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to enrollment.
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  • Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC.
  • Any prior cancer treatment must be completed at least 6 months prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline. NOTE: a single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to enrollment. NOTE: Extracranial radiation is allowed.
  • A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
  • Demonstrate adequate organ function as defined in the table below
  • Absolute Neutrophil Count (ANC) ≥ 1.5K/mm3 without GCSF
  • Hemoglobin (Hgb) ≥ 9 g/dL (without transfusion)
  • Lymphocyte Count: ≥ 500/µL
  • Platelet Count: ≥ 100,000/µL without transfusion
  • Calculated creatinine clearance ≥ 50 cc/min OR Serum Cr < 1.5 x institutional ULN
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN with liver metastasis
  • Alanine aminotransferase (ALT) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN with liver metastasis
  • Females of childbearing potential must have a negative serum pregnancy test within 3 days (72 hours) prior to enrollment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception, including at least one method with a failure of < 1% per year, from the time of informed consent until 150 days (5 months) after treatment discontinuation.
  • Negative hepatitis B surface antigen (HBsAg) test, negative total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. Testing required at screening only if results are not known.
  • Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test. The HCV RNA test will be performed only for patients who have a positive HCV antibody test. A positive HCV RNA test is sufficient to diagnose active HCV infection in the absence of an HCV antibody test.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures.

Who cannot join

  • Known active CNS metastases which are symptomatic. CNS metastases are considered asymptomatic if the patient does not require high dose or escalating corticosteroids or anticonvulsant therapy. Steroid dose must be equivalent to 2 mg of dexamethasone or less daily.
  • Prior steroid use as part of an anti-emetic regimen with chemotherapy is allowed.
  • Patients must be on a stable dose of corticosteroid. No tapering or decreasing dose within 7 days of enrollment.
  • Leptomeningeal disease. Discrete dural-based metastases will be allowed without evidence of leptomeningeal disease.
  • Radiation therapy within 14 days prior to Day 1 of Cycle 1 Day 1. NOTE: Extracranial radiation is allowed.
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
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  • Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone < 10 mg daily (or equivalent).
  • History of interstitial pneumonitis from any cause.
  • Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study as assessed by site investigator.
  • Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on Cycle 1 Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible. NOTE: Subjects with active tuberculosis are NOT eligible.
  • Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead.
  • History of myocardial infarction, NYHA class II or greater congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.
  • Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), Testing not required at screening.
  • Requirement for ongoing anticoagulation with heparin, low molecular weight heparin, or other oral anticoagulant (coumadin, DOAC).
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). NOTE: Patients with indwelling catheters (e.g., PleurX®) are allowed.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
  • History of allergic reactions to carboplatin or etoposide.
  • Intolerance of atezolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
  • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
  • Rash must cover < 10% of body surface area
  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
  • There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Treatment with any investigational drug within 28 days prior to Cycle 1 Day 1.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • St. Vincent Anderson Regional Hospital

    Anderson, Indiana, 46016

  • Summit Health

    Berkeley Heights, New Jersey, 07922

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612

  • City of Hope

    Duarte, California, 91010

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

Other trials in United States

About this study

This is a single arm, multicenter phase II trial for 60 patients with untreated extensive stage (ES) small cell lung cancer (SCLC) with asymptomatic brain metastases. Subjects will receive 4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) and etoposide (80-100 mg/m2 on Days 1-3). Each cycle equals 21 days. After 4 cycles of induction treatment, subjects will receive atezolizumab maintenance 1200 mg on Day 1 of each 3-week cycle. Subjects will receive treatment until disease progression, unacceptable drug-related toxicity, or withdrawal from study for any reason.

Medical subject headings
Small Cell Lung Carcinoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called paraplatin

    Carboplatin 5-6 mg/mL/min AUC will be delivered over 30 - 60 minutes intravenously on Day 1 of each 21 day Cycle after completion of atezolizumab. For 4 cycles.

  • EtoposideDrug

    Also called VP-16

    Etoposide 80-100 mg/m2 will be delivered over 60 minutes intravenously on Days 1-3 of each 21 day Cycle after completion of carboplatin (Day 1 only). For 4 cycles.

  • AtezolizumabDrug

    Also called Imfinzi

    Atezolizumab 1200 mg will be delivered over 60 (± 15) minutes intravenously on Day 1 of each 21 day Cycle for 4 cycles then continue as monotherapy maintenance with the same schedule.

Study groups in NCT04610684
Study groupRoleWhat they receive
Study Treatment ArmExperimental4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) and etoposide (80-100 mg/m2 on Days 1-3). After 4 cycles of induction treatment, subjects will receive atezolizumab maintenance 1200 mg on Day 1 of each 3-week cycle.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intracranial Progression Free Survival (iPFS)

    Intracranial PFS is defined as the time from Day 1 of treatment until the criteria for intracranial disease progression is met as defined by RANO-BM or death as a result of any cause, whichever comes first. Progression disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: From C1D1 until death or up to a maximum of 6 months

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    ORR will include complete response (CR) + partial response (PR) as determined by RECIST 1.1. Complete response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From C1D1 until death or up to a maximum of 6 months

  2. Extracranial Progression Free Survival (PFS)

    Extracranial PFS is defined as the time from Day 1 of treatment until the criteria for extracranial disease progression is met as defined by RECIST 1.1 or death as a result of any cause, whichever comes first.Progression disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: From C1D1 until death or up to a maximum of 6 months

  3. Overall Survival (OS)

    OS is defined as the time from Day 1 of treatment until death as a result of any cause.

    Measured: From C1D1 until death or up to a maximum of 9 months

  4. Toxicity of Atezolizumab Plus Carboplatin and Etoposide

    Toxicity of atezolizumab has been evaluated when administered with carboplatin and etoposide in subjects with untreated SCLC brain metastases.Toxicity will be graded by Common Toxicity Criteria for Adverse Events (CTCAE V5).

    Measured: From C1D1 until death or up to a maximum of 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2020
  2. Study start5 Jan 2021
  3. Primary completion15 Jul 2022
  4. Study completion20 Sep 2022

Why it stopped: Lack of Enrollment

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04610684
Sponsor's protocol ID
HCRN LUN19-427
Status last verified
Feb 2024
First submitted
26 Oct 2020
Last updated
13 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Etoposide and Atezolizumab in people with Small-cell Lung Cancer and Brain Metastases, run by Jeffrey Clarke at 6 sites in United States.

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 23 inclusion and 29 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 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 13 Mar 2024). 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?

Intracranial Progression Free Survival (iPFS) (time frame: From C1D1 until death or up to a maximum of 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04610684.

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 13 Mar 2024.

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