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Non-small Cell Lung Cancer Stage IVPhase 2ATEZO-BRAINNCT03526900

Atezolizumab in Combination With Carboplatin Plus Pemetrexed in Chemotherapy-naïve Patients With Asymptomatic Brain Metastasis

A Phase 2 study testing Atezolizumab in people with Non-small Cell Lung Cancer Stage IV, run by Spanish Lung Cancer Group at 15 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter, national, nonrandomized, phase II trial in subjects with nonsquamous NSCLC patients that have untreated asymptomatic BM. A pre-screening period using brain MRI for patients diagnosed with advanced non-squamous NSCLC EGFR/ALK wild type and ECOG PS 0-1 will be crucial to identify patients with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer Stage IV
What is being tested?
Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
15 sitesSpain
Study dates
7 Jul 2018to 15 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

  • Patients aged 18 years or older.
  • Signed written informed consent.
  • ECOG Performance Status (PS) of 0 to 1.
  • Subjects with histologically or cytologically confirmed stage IV non-squamous NSCLC who did not received any prior chemotherapy or brain radiotherapy. Patients with EGFR mutation or ALK fusion will be excluded.
  • Patients who received prior neo-adjuvant, adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months since the last dose of chemotherapy and/or radiotherapy.
  • Asymptomatic or oligosymptomatic(considered to have alterations in the neurological examination, whether or not they are noted in the anamnesis, that do not prevent appropriate functioning according to the patients' basal state, or that disappear with medical treatment (corticosteroids, analgesics, anticonvulsants) untreated brain metastases.
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  • Steroids treatment (dexamethasone) is allowed and patients that remained oligosymptomatic or asymptomatic for 2 weeks on steroids will be eligible when they were receiving ≤ 4mg dexamethasone once a day.
  • Systemic measurable disease by computed tomography (CT) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria AND brain measurable disease by magnetic resonance imaging (MRI) per RANO-BM criteria.
  • Availability of a formalin-fixed paraffin-embedded block (cell blocks will be accepted if tumor biopsy is not available) containing tumor tissue or 10 unstained slides.
  • Adequate hematopoietic, hepatic and renal function:
  • ANC ≥ 1,500 cells/μL o Lymphocyte count ≥ 500 cells/μL o Platelet count ≥ 100,000 cells μL o Hemoglobin ≥ 9.0 g/dL (transfusion are is allowed) o INR or aPTT ≤ 1.5 x upper limit of normal (ULN); patients receiving therapeutic anticoagulation should be on a stable dose o ALT, AST and/or alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions: -patients with known liver metastasis: ALT and/or AST ≤ 5 x ULN -patients with known bone metastasis: alkaline phosphatase ≤ 5 x ULN o Serum bilirubin ≤ 1.5 x ULN; patients with known Gilbert disease who have serum bilirubin ≤ 3 x ULN may be recruited) o Calculated creatinine clearance (CRCL) ≥ 45 mL/min (based on the standard Cockcroft and Gault formula).
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive non-hormonal methods with a failure rate of 1% per year during the treatment period and for 3 months after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, 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). Examples of non-hormonal contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization and copper intrauterine devices.
  • For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 3 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

Who cannot join

  • History of other malignancy within 3 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
  • Patients harboring an EGFR mutation or an ALK fusion will be excluded
  • Leptomeningeal carcinomatosis or metastases in the brain stem, mid-brain, pons, medulla or lesions causing obstructive hydrocephalus
  • Patients with neurological symptoms, including those receiving > 4mg of dexamethasone will not be eligible for this study
  • Spinal or hemorrhagic metastases will be excluded
  • Prior surgical resection of brain or spinal lesions in the prior 14 days
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  • Previous systemic treatment or neo-adjuvant or adjuvant chemotherapy less than 6 months before enrollment
  • Clinical significant comorbidities that impaired administration of platinum-based chemotherapy
  • History of autoimmune disease, including but not limited to myasthenia gravis, myosistis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren 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 are eligible for this study
  • Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin are eligible for this study
  • Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriasic arthritis would be excluded) are permitted provided that they meet the following conditions: rash covers less than 10% of body surface area, disease is well controlled at baseline and only requires lowpotency topical steroids, no acute exacerbations during the last 12 months
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis or active radiation pneumonitis out of the radiation field
  • Previous treatment with immune checkpoint inhibitors or CD137 and OX-40 agonists
  • Treatment with investigational therapy within 28 days prior to initiation of study drug - Positive for hepatitis C virus (HCV) antibody or for hepatitis B surface antigen (HBsAg) at screening. Patients with past or resolved hepatitis B virus (HBV) infection (HBcAb positive with absence of HBsAg) would be eligible whether they are negative for HBV DNA. Patients positive for HCV antibody would be eligible whether they are negative for HCV RNA
  • Active tuberculosis or HIV infection
  • Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment.
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Spain15 sites

  • Complejo Hospitalario de la Coruña

    A Coruña, Coruña, 15006

  • Hospital General de Alicante

    Alicante, 03010

  • Hospital Universitari Germans Tries i Pujol

    Badalona, Barcelona, 08916

  • H.U.Vall D´Hebrón

    Barcelona, 08035

  • Hospital de Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital General Universitario de Elche

    Elche, Alicante, 03203

  • Hospital Dr. Josep Trueta

    Girona, 17007

  • Hospital Universitari de Bellvitge

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Insular de Gran Canaria

    Las Palmas de Gran Canaria, Las Palmas

  • Hospital Fundación Jiménez Díaz

    Madrid, 28040

  • H. La Paz

    Madrid

  • Hospital General Universitario de Valencia

    Valencia, 46014

  • Hospital La Fe

    Valencia, 46026

  • Hospital Clínico Universitario de Valladolid

    Valladolid, 47003

  • Complexo Hospitalario Universitario de Vigo

    Vigo, Pontevedra, 36036

Other trials in Spain

About this study

Official title: Phase II Non-randomized Study of a Atezolizumab (MPDL3280A) in Combination With Carboplatin Plus Pemetrexed in Patients Who Are Chemotherapy-naïve and Have Stage IV Non-squamous Non-small Cell Lung Cancer Twith Asymptomatic Brain Metastasis

This is a multicenter, national, nonrandomized, phase II trial in subjects with nonsquamous NSCLC patients that have untreated asymptomatic BM. A pre-screening period using brain MRI for patients diagnosed with advanced non-squamous NSCLC EGFR/ALK wild type and ECOG PS 0-1 will be crucial to identify patients with asyntomatic BM. Forty patients will be recruited.

Read the detailed description

Atezolizumab will be administered intravenously (iv) at a dose of 1200 mg over 60 minutes on day 1 of each cycle. The subsequent cycles of atezolizumab can be administered over 30 minutes, if there were no infusion-related toxicities. Pemetrexed will be administered at a dose of 500 mg/m2 iv over 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4mg bid will be administered one day before and after pemetrexed treatment. Carboplatin will be administered at a dose with an area under the curve of 5 over 30 minutes on day 1 of each cycle approximately 30 minutes after the end of the pemetrexed infusion. After completing 4 to 6 cycles of carboplatin plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab until unacceptable toxicity, disease progression, patient/physician decision or completion of 2 years of therapy.

Tumor measurements by CT scan (systemic response) and brain MRI (intracranial response) will be performed every 6 weeks until the 12th week and thereafter every 9 weeks until disease progression. In case of brain progression, rescue with brain radiotherapy should be considered. In case of exclusive brain progression, patients are allowed to receive brain radiotherapy (WBRT or SRS) and then continue with study therapy if the patients maintain clinical benefit and appropriate performance status (ECOG PS≤2).Immunotherapy should be started no later than 4 weeks after completing radiation therapy (brain radiotherapy 2 weeks + 4 weeks of recovery from potential acute toxicity). In case of systemic progression without brain progression, a novel line of systemic treatment should be considered. Patients experiencing systemic progression and/or brain progression will be followed and two post-progression visits will be performed at 30 and 90 days.

Response will be assessed independently in the brain and systemically: systemic response will be evaluated according to RECIST v1.1 and brain response according to the RANO response assessment criteria for BM (RANO-BM). Adverse events will be assessed throughout and assessed using the CTCAE version 4.03. EORTC quality of life questionnaire EORTC C30 and the submodules QLQ-LC13 and BN20 will be assessed in the ITT population at baseline, cycle 5 (week 12),cycle 9 (week 24), at end of study treatment (30 and 90 days) and/or at disease progression. Periodic evaluations of the trial data will be conducted by an independent DMC to ensure subject safety and to evaluate the efficacy at the interim analyses. Neurocognitive assessment including the standardized neuropsychological tests: Hopkins Verbal Learning Test (HVLT), Trail Making Test (TMT), Rey-Osterrieth complex figure test (ROCF) and Controlled Oral Word Association Test (COWA) will be assessed at baseline cycle 5 (week 12),cycle 9 (week 24), at end of study treatment (30 and 90 days) and/or at disease progression.

Being tested
Atezolizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq

    • Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2
    • Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
Study groups in NCT03526900
Study groupRoleWhat they receive
AtezolizumabExperimentalInduction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Receives: Drug: Atezolizumab

What is being measured

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

  1. Efficacy of Atezolizumab + CBDCA + Pemetrexed by Evaluating PFS Rate

    Percentage of subjects without disease progression (intracranial or systemic) at 12 weeks after enrollment. Determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:Complete Response(CR),Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR) Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions;Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions

    Measured: 12 weeks after enrollment

Secondary outcomes (1)

  1. Efficacy of Atezolizumab + CBDCA + Pemetrexed by Measuring Objective Response.

    Objective response defined as a complete response or partial response on two consecutive evaluations 6 weeks apart, as determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR), Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions; Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions or the appearance of new lesions

    Measured: Two consecutive evaluations 6 weeks apart

Timeline

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

  1. First posted16 May 2018
  2. Study start7 Jul 2018
  3. Primary completion31 Mar 2022
  4. Study completion15 Sep 2022

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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03526900
Sponsor's protocol ID
GECP 17/05_ATEZO-BRAIN
Other IDs
2017-005154-11, 2017
Acronym
ATEZO-BRAIN
Status last verified
Oct 2024
First submitted
18 Apr 2018
Last updated
9 Oct 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Nadal E, Rodriguez-Abreu D, Simo M, Massuti B, Juan O, Huidobro G, Lopez R, De Castro J, Estival A, Mosquera J, Sullivan I, Felip E, Blasco A, Guirado M, Pereira E, Vilarino N, Navarro V, Bruna J. Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05). J Clin Oncol. 2023 Oct 1;41(28):4478-4485. doi: 10.1200/JCO.22.02561. Epub 2023 Aug 21.

    PubMed 37603816

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab in people with Non-small Cell Lung Cancer Stage IV, run by Spanish Lung Cancer Group at 15 sites in Spain.

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 13 inclusion and 18 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: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Spain. 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 9 Oct 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?

Efficacy of Atezolizumab + CBDCA + Pemetrexed by Evaluating PFS Rate (time frame: 12 weeks after enrollment). 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 NCT03526900, which also lists 1 linked publication.

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 9 Oct 2024.

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