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Small-cell Lung CancerPhase 2NCT04923776

Liver Directed RT + Chemo-immunotherapy for ES-SCLC

A Phase 2 study testing Carboplatin, Etoposide and Atezolizumab in people with Small-cell Lung Cancer, run by Brian Henick, MD at 1 site in United States.

Terminated

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

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate whether radiation treatment directed at liver metastases can be safely added to standard of care treatment for extensive stage small cell lung cancer (ES-SCLC). 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?
Carboplatin, Etoposide and Atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
20 Sep 2021to 23 Dec 2023
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

  • Age≥ 18 years
  • Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group (VALG) staging system)
  • No prior treatment for ES-SCLC
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Patients with a history of treated, asymptomatic CNS metastases are eligible providing they meet the following criteria
  • Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord)
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  • No ongoing requirement for corticosteroids as therapy for CNS disease
  • No stereotactic brain radiation within 7 days
  • No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
  • Patients with new asymptomatic Central Nervous System (CNS) metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to randomization, if all other criteria are met.
  • At least one liver metastasis measuring 1 cm.
  • Measurable disease, as defined by RECIST v1.1, in addition to the liver lesion(s) to which SBRT is planned.
  • Patients must submit a pre-treatment tumor tissue sample from a liver metastasis. Tumor tissue must be obtained prior to the start of treatment.
  • Adequate hematologic and end organ function, defined by the following laboratory results:
  • Absolute neutrophil count (ANC) ≥1500 cells/μL without granulocyte colony-stimulating factor support
  • Lymphocyte count ≥500/μL
  • Platelet count ≥100,000/μL without transfusion
  • Hemoglobin ≥9.0 g/dL Patients may be transfused to meet this criterion.
  • International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (aPTT) ≤1.5×upper limit of normal (ULN) This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), and alkaline phosphatase ≤5×ULN
  • Serum bilirubin ≤1.25×ULN (Patients with known Gilbert disease who have serum bilirubin level ≤3×ULN may be enrolled)
  • Serum creatinine ≤1.5×ULN
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods as defined below:
  • Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of carboplatin and etoposide
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
  • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
  • With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during treatment with chemotherapy (i.e., carboplatin and etoposide) and for at least 6 months after the last dose of chemotherapy to avoid exposing the embryo.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable methods of contraception.
  • Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible, provided they are stable on anti-retroviral therapy, have a CD4 count3 200/µL, and have an undetectable viral load
  • Ability to understand and the willingness to sign a written informed consent document.
  • Ability to comply with the study protocol, in the investigator's judgment.

Who cannot join

  • Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • 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 randomization
  • Leptomeningeal disease
  • Prior radiation treatment of SCLC outside of the CNS
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed.
  • Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium >ULN)
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  • Patients who are receiving denosumab prior to randomization must be willing and eligible to discontinue its use and replace it with a bisphosphonate while in the study.
  • Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS >90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
  • Prior radiation for non-SCLC malignancies >5 years prior to randomization will be permitted, with the exception of those who underwent liver-directed treatments
  • Child-Pugh class B cirrhosis or worse
  • History of liver-directed ablative therapy for any indication, including radiation, chemoembolization, radiofrequency ablation, or other similar modalities
  • Women who are pregnant, lactating, or intending to become pregnant during the study
  • Pregnant women are excluded from this study because carboplatin and etoposide are category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab.
  • 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 autoimmune disease, including but not limited to myasthenia gravis, myositis,autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
  • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Rash must cover less than 10% of body surface area
  • Disease is well controlled at baseline and only requires low potency topical steroids
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation (PUVA), methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency, or oral steroids)
  • 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 (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
  • Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen (HBsAg) test at screening) or hepatitis C
  • Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody (HBcAb) and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomization.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Active tuberculosis
  • Severe infections at the time of enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina (Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate).
  • Major surgical procedure other than for diagnosis within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
  • Prior allogeneic 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 patient at high risk for treatment complications
  • Previous anti-cancer therapy for ES-SCLC
  • Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment
  • Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere and approximately April through September in the Southern Hemisphere).
  • Patients must agree not to receive live, attenuated influenza vaccine (e.g.,FluMist®) within 28 days prior to randomization, during treatment or within 90 days following the last dose of atezolizumab/placebo.
  • Prior treatment with immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1therapeutic antibodies
  • Treatment with systemic immunosuppressive medications (including, but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to randomization
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Principal Investigator
  • The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
  • History of allergic reactions to carboplatin or etoposide

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: A Phase II Trial of Atezolizumab + Carboplatin + Etoposide With Liver-Directed Radiotherapy (RT) in Extensive Stage Small Cell Lung Cancer (ES-SCLC) Patients With Liver Metastases

The purpose of this study is to evaluate whether radiation treatment directed at liver metastases can be safely added to standard of care treatment for extensive stage small cell lung cancer (ES-SCLC). The current standard treatment for people who have ES-SCLC is chemotherapy including drugs called carboplatin and etoposide, that is combined with a type of immunotherapy called atezolizumab. However, patients with liver involvement of their ES-SCLC don't respond as well to this treatment. The study aims to answer whether adding radiation directed at liver metastases can improve responses to standard chemo-immunotherapy in this patient population. All study participants will get the same study intervention, which will be chemo-immunotherapy and radiation therapy.

Read the detailed description

Although the clinical evidence for the combination of radiation therapy and immunotherapy is more limited, numerous case reports, retrospective studies, early stage trials, and ongoing prospective trials highlight the potential for combining radiation with immunotherapy in augmenting the anti-tumor response.

The combination of stereotactic body radiation therapy (SBRT) of liver lesions with immunotherapy has been less well studied. Given the findings that patients with ES-SCLC and liver involvement have a poor prognosis and a limited response to chemo-immunotherapy, the investigators aim to augment the systemic anti-tumor immune response with RT targeted to liver metastases administered in addition to standard of care treatment. Preclinical data and prior clinical studies support the reasoning for these treatment approaches, and the investigators hypothesize that combination RT with chemo-immunotherapy will lead to improved local control and progression free survival in ES-SCLC patients with liver involvement.

Being tested
Carboplatin, Etoposide, Atezolizumab, Stereotactic Body Radiation Therapy (SBRT)
Keywords
Liver metastases, Radiation chemotherapy, Radiotherapy
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.

  • CarboplatinDrug

    Also called Paraplatin

    The dosage for this drug is area under the curve (AUC) 5 mg/ml/min intravenous, Day 1, every 21 days for 4 cycles. This is standard of care.

  • EtoposideDrug

    Also called Vepesid

    The dosage for this drug is 100 mg/m2 Intravenous, Days 1-3, every 21 days for 4 cycles. This is standard of care.

  • AtezolizumabDrug

    Also called Tecentriq

    The dosage for this drug is 1200 mg Intravenous, Day 1, every 21 days until disease progression. This is standard of care.

  • Stereotactic Body Radiation Therapy (SBRT)Radiation

    This radiotherapy is given within +/-3 days of cycle 2, 10 Gy 3 doses on alternating days. This is not standard of care and considered interventional.

Study groups in NCT04923776
Study groupRoleWhat they receive
Experimental: Chemotherapy+SBRTExperimentalAddition of SBRT, directed at liver metastases, to standard of care (SOC) treatment atezolizumab+chemotherapy in SCLC. All patients must undergo a mandatory biopsy of a liver lesion prior to chemotherapy initiation. Cycle 1 of chemoimmunotherapy will be administered as per standard of care, with radiation planning to be done subsequently in anticipation of liver-directed SBRT.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

What is being measured

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

  1. Progression Free Survival (PFS) Rate

    Progression free survival rate at 6 months will be measured to assess the efficacy of liver-directed SBRT when added to standard of care atezolizumab + chemotherapy. 6-month PFS rate will be defined as the proportion of patients that are progression free and alive at 6 months from the start of treatment.

    Measured: Up to 6 months

Secondary outcomes (2)

  1. Overall Survival Rate

    Overall survival (OS) will be defined as the time from treatment start to date of death or last follow up. Patients lost to follow-up at the cut-off date will be censored in the analysis.

    Measured: Up to 2 years

  2. Disease Control Rate (DCR)

    Disease control rate (DCR) will be defined as the proportion of patients who have a partial (PR) or complete response (CR) or stable disease (SD) after beginning study treatment. Only patients who have received at least one cycle of therapy and have had their disease re-evaluated will be considered evaluable for response.

    Measured: Up to 2 years

Timeline

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

  1. First posted11 Jun 2021
  2. Study start20 Sep 2021
  3. Primary completion13 Sep 2023
  4. Study completion23 Dec 2023

Why it stopped: Poor 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
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04923776
Sponsor's protocol ID
AAAT0174
Status last verified
Dec 2024
First submitted
7 Jun 2021
Last updated
30 Dec 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, run by Brian Henick, MD at 1 site 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 33 inclusion and 42 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 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 30 Dec 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?

Progression Free Survival (PFS) Rate (time frame: Up to 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 NCT04923776.

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 30 Dec 2024; AzTrials last refreshed its copy on 29 Oct 2026.

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