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NSCLC Stage IVPhase 2NCT03713944

Carboplatin Plus Pemetrexed Plus Atezolizumab Plus Bevacizumab in Chemotherapy and Immunotherapy-naïve Patients With Stage IV Non-squamous Non-small Cell Lung Cancer

A Phase 2 study testing Carboplatin, Pemetrexed and Atezolizumab in people with NSCLC Stage IV and NSCLC, Recurrent, run by Nasser Hanna at 7 sites 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

This is a multicenter single arm phase II clinical trial. All eligible patients will receive: Carboplatin (AUC 5) i.v. day 1 plus pemetrexed (500 mg/m2) i.v. day 1 plus atezolizumab 1200 mg i.v. day 1 plus bevacizumab 15 mg/kg i.v. day 1 every 3 weeks for up to 4 cycles. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC Stage IV, NSCLC, Recurrent
What is being tested?
Carboplatin, Pemetrexed and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
7 sitesUnited States
Study dates
15 Nov 2018to 16 Dec 2021
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. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of 0-1 within 28 days prior to registration.
  • Must have life expectancy of > 3 months at time of consent
  • Histological or cytological confirmation of non-squamous NSCLC.
  • Must have known PD-L1 status using the Dako 22C3 antibody (+ vs. -) OR must have at least 5 unstained slides to perform PD-L1 testing (results not required for eligibility). PD-L1 positive is defined as a tumor proportion score (TPS) ≥ 1%. PD-L1 negative is defined as a TPS <1%.
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  • Patients with known targetable mutations in EGFR or BRAF or known translocations in ALK or ROS1 are eligible if they have received FDA approved targeted therapy first. A 1-week washout prior to enrollment is strongly encouraged (3 weeks preferred).
  • Stage IV disease or recurrent disease
  • Measurable disease according to RECIST v1.1 criteria within 28 days prior to registration with either PET/CT scan, CT scan of chest and abdomen, or CT chest including upper abdomen and adrenal glands which define stage IV disease.
  • Patients who had disease progression greater than 1 year after completing prior adjuvant therapy for stage I - III are eligible as long as no systemic therapy was given for recurrence.
  • No prior immunotherapy or antiangiogenic therapy.
  • Prior platinum therapy or pemetrexed are permissible if previously given in the adjuvant setting for stage I-III disease and disease recurrence is > 1 year from completion of therapy.
  • If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  • Demonstrate adequate organ function as defined below, with all screening labs to be obtained within 28 days prior to registration
  • Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Platelets ≥ 100 K/mm3
  • Serum creatinine: ≤1.5 X upper limit of normal (ULN) OR Calculated Creatinine Clearance: ≥ 40 cc/min using the Cockcroft-Gault formula
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 1.5 × ULN or < 5x ULN if the transferase elevation was due to liver metastases
  • Alanine aminotransferase (ALT) ≤ 1.5 × ULN or <5x ULN if the transferase elevation was due to liver metastases
  • International Normalized Ratio (INR) or Prothrombin Time (PT) \& aPTT ≤ 1.5 × ULN (unless subjects is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
  • Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: 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).
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two non-hormonal methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for 5 months after the last dose of atezolizumab or 120 days after the last dose of any study drug, whichever is later;
  • examples of non-hormonal 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. Must use "estrogen-free" hormonal method if this is chosen contraception method.
  • A barrier method may be used as the second contraceptive method. 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 acceptable methods of contraception.
  • Contraception method must begin starting from the time of informed consent until 120 days after treatment discontinuation.
  • 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 the treatment period and for 120 days after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
  • 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 acceptable methods of contraception.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Who cannot join

  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Active secondary cancers.
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Brain imaging with either MRI or CT with contrast must be performed on all subjects at screening to evaluate for the presence of brain metastases. Patients with a history of treated CNS lesions are eligible, provided that all of the following criteria are met:
  • Measurable disease, per RECIST v1.1, must be present outside the CNS.
  • The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
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  • Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
  • The patient has not received stereotactic radiotherapy within 14 days prior to initiation of study treatment or whole-brain radiotherapy within 21 days prior to initiation of study treatment
  • The patient has no ongoing requirement for corticosteroids as therapy for CNS disease and off steroid therapy for at least 14 days. Anticonvulsant therapy at a stable dose is permitted.
  • Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
  • Major surgery within 3 weeks of the first dose of trial treatment.
  • Completed palliative radiotherapy within 7 days of the first dose of trial treatment.
  • The patient had a history of uncontrolled hereditary or acquired thrombotic disorder.
  • Patients with a history of gross hemoptysis (defined as bright red blood or ≥1/2 teaspoon) within 2 months prior to enrollment.
  • The patient had clinically relevant congestive heart failure (CHF; NYHA II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
  • The patient had experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
  • The patient had uncontrolled arterial hypertension ≥150 / ≥90 mm Hg despite standard medical management.
  • The patient has had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
  • Patients with ≥ 2 + protein on dipstick urinalysis. All patients with ≥ 2 + protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours to be eligible.
  • Clear cavitation of pulmonary lesions seen on imaging.
  • The patient had significant bleeding disorders, vasculitis, or experienced Grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollment.
  • History of GI perforation and/or fistulae within 6 months prior to enrollment.
  • Evidence of tumor invading or abutting major blood vessels.
  • The patient had a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
  • Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  • Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
  • Has active autoimmune disease that has required systemic treatments in the past 2 years, including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents; chronic or occasional use of low-dose steroid therapy can be still be considered eligible as long as no greater than the daily equivalent of 5mg oral prednisone.
  • Exceptions to excluding patients with active autoimmune disease include the following:
  • 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 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
  • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
  • Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects on chronic systemic steroids would be excluded from the study.
  • Had prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication (including, but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions:
  • Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
  • Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
  • Treatment with denosumab (a RANKL inhibitor) within 4 weeks prior to initiation of study treatment. Patients receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate during atezolizumab treatment.
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay. For patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg), the patient is only eligible if they are negative for HBV DNA.
  • Active tuberculosis
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has known interstitial lung disease or history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted. Lymphangitic spread of the NSCLC is not exclusionary.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612

  • Indiana Univeristy Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Wisconsin

    Madison, Wisconsin, 53705

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • ProHealth Care

    Waukesha, Wisconsin, 53188

Other trials in United States

About this study

Official title: A Phase II Study of Carboplatin Plus Pemetrexed Plus Atezolizumab Plus Bevacizumab in Chemotherapy and Immunotherapy-naïve Patients With Stage IV Non-squamous Non-small Cell Lung Cancer: Big Ten Cancer Research Consortium BTCRC-LUN17-139

This is a multicenter single arm phase II clinical trial. All eligible patients will receive:

Carboplatin (AUC 5) i.v. day 1 plus pemetrexed (500 mg/m2) i.v. day 1 plus atezolizumab 1200 mg i.v. day 1 plus bevacizumab 15 mg/kg i.v. day 1 every 3 weeks for up to 4 cycles.

Patients with non-PD after 4 cycles will be permitted to continue with maintenance therapy with pemetrexed plus atezolizumab plus bevacizumab every 3 weeks until the time of disease progression or intolerable toxicities.

Read the detailed description

The hypothesis of this study is that the addition of Atezolizumab (an anti-PD-L1 antibody), to the combination of Carboplatin plus Pemetrexed plus Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, for the treatment of patients with stage IV non-squamous, non-small cell lung cancer (NSCLC) will improve progression free survival (PFS) compared with a historical control of carboplatin plus pemetrexed plus bevacizumab.

Medical subject headings
Carcinoma, Non-Small-Cell Lung, Recurrence

What participants receive

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

Study groups in NCT03713944
Study groupRoleWhat they receive
Carboplatin, Pemetrexed, Atezolizumab plus BevacizumabExperimentalCarboplatin (AUC 5) i.v. day 1 plus pemetrexed (500 mg/m2) i.v. day 1 plus atezolizumab 1200 mg i.v. day 1 plus bevacizumab 15 mg/kg i.v. day 1 every 3 weeks for up to 4 cycles. Patients with non-PD after 4 cycles will be permitted to continue with maintenance therapy with pemetrexed plus atezolizumab plus bevacizumab every 3 weeks until the time of disease progression or intolerable toxicities.
Receives: Drug: Carboplatin; Drug: Pemetrexed; Drug: Atezolizumab; Drug: Bevacizumab

What is being measured

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

  1. Progression Free Survival

    Progression free survival (PFS) defined as the time from the initiation of treatment to the time when the criteria for disease progression is met as defined by RECIST v1.1 or death of any cause.Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: From C1D1 until progression or death up to maximum of 20 Months

Secondary outcomes (4)

  1. Overall Response Rate

    Overall Response rate will include confirmed complete response (CR) + confirmed partial response (PR), as determined as per RECIST v1.1 criteria and assessed by the local investigator or designee.

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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; Overall Response (OR) = CR + PR.

    Measured: From C1D1 until death or up to a maximum of 28 months.

  2. Disease Control Rate

    Disease control rate will include complete response (CR], partial response (PR), and stable disease (SD), as per RECIST v1.1 criteria.

    Measured: From C1D1 until death or up to a maximum of 28 months

  3. Overall Survival

    To estimate the overall survival (OS) of carboplatin plus pemetrexed plus atezolizumab plus bevacizumab in immunotherapy and chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer.

    Measured: From C1D1 up to a maximum of 28 Months or until death

  4. Number of Participants With Adverse Events

    To characterize the toxicity of carboplatin plus pemetrexed plus atezolizumab plus bevacizumab in immunotherapy and chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.

    Measured: From C1D1 up to a maximum of 20 Months or until death

Timeline

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

  1. First posted22 Oct 2018
  2. Study start15 Nov 2018
  3. Primary completion16 Dec 2021
  4. Study completion16 Dec 2021

Why it stopped: Extreme toxicity, thromboembolic events

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
Model description
Single Arm Therapeutic study using historical controls
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03713944
Sponsor's protocol ID
BTCRC-LUN17-139
Status last verified
Feb 2023
First submitted
18 Oct 2018
Last updated
1 Mar 2023
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, Pemetrexed and Atezolizumab in people with NSCLC Stage IV and NSCLC, Recurrent, run by Nasser Hanna at 7 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 31 inclusion and 49 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 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 1 Mar 2023). 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 (time frame: From C1D1 until progression or death up to maximum of 20 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 NCT03713944.

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 1 Mar 2023.

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