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SWOG S1827 (MAVERICK) Testing Whether the Use of Brain Scans Alone Instead of Brain Scans Plus Preventive Brain Radiation Affects Lifespan in Patients With Small Cell Lung Cancer

NCT04155034

Description:

This phase III trial studies magnetic resonance imaging (MRI) surveillance and prophylactic cranial irradiation (PCI) to see how well they work compared to MRI surveillance alone in treating patients with small cell lung cancer. MRI scans are used to monitor the possible spread of the cancer with an MRI machine over time. PCI is radiation therapy that is delivered to the brain in hopes of preventing spread of cancer into the brain. The use of brain MRI alone may reduce side effects of receiving PCI and prolong patients' lifespan. Monitoring with MRI scans alone (delaying radiation until the actual spread of the cancer) may be at least as good as the combination of PCI with MRI scans.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: SWOG S1827 (MAVERICK) Testing Whether the Use of Brain Scans Alone Instead of Brain Scans Plus Preventive Brain Radiation Affects Lifespan in Patients With Small Cell Lung Cancer
  • Official Title: MRI Brain Surveillance Alone Versus MRI Surveillance and Prophylactic Cranial Irradiation (PCI): A Randomized Phase III Trial in Small-Cell Lung Cancer (MAVERICK)

Clinical Trial IDs

  • ORG STUDY ID: S1827
  • SECONDARY ID: NCI-2019-05338
  • SECONDARY ID: S1827
  • SECONDARY ID: S1827
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT04155034

Conditions

  • Extensive Stage Lung Small Cell Carcinoma
  • Limited Stage Lung Small Cell Carcinoma
  • Lung Small Cell Carcinoma

Purpose

This phase III trial studies magnetic resonance imaging (MRI) surveillance and prophylactic cranial irradiation (PCI) to see how well they work compared to MRI surveillance alone in treating patients with small cell lung cancer. MRI scans are used to monitor the possible spread of the cancer with an MRI machine over time. PCI is radiation therapy that is delivered to the brain in hopes of preventing spread of cancer into the brain. The use of brain MRI alone may reduce side effects of receiving PCI and prolong patients' lifespan. Monitoring with MRI scans alone (delaying radiation until the actual spread of the cancer) may be at least as good as the combination of PCI with MRI scans.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate whether overall survival (OS) with magnetic resonance imaging (MRI)
      surveillance alone is not inferior to MRI surveillance combined with prophylactic cranial
      irradiation (PCI) for the treatment of small cell lung cancer (SCLC).

      SECONDARY OBJECTIVES:

      I. To compare cognitive failure free survival (CFFS) rate up to 12 months after randomization
      between the arms.

      II. To compare brain-metastasis-free survival between the arms. III. To compare OS between
      the arms within the subgroups of patients with limited-stage and extensive-stage disease.

      IV. To compare cognitive failure free survival (CFFS) rates at the assessment times between
      the arms.

      V. To compare the cumulative incidence of cognitive failure with death as a competing risk
      between the arms.

      VI. To compare the frequency and severity of toxicities between the two arms.

      ADDITIONAL OBJECTIVE:

      I. To collect blood for banking.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients undergo conventional or hippocampal avoidance PCI over 20 minutes 5 days per
      week for 2 weeks. Patients also undergo MRI scan at 3, 6, 9, 12, 18, and 24 months.

      ARM II: Patients undergo MRI scan at 3, 6, 9, 12, 18, and 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (PCI, MRI)Active ComparatorPatients undergo conventional or hippocampal avoidance PCI over 20 minutes 5 days per week for 2 weeks. Patients also undergo MRI scan at 3, 6, 9, 12, 18, and 24 months.
    Arm II (MRI)ExperimentalPatients undergo MRI scan at 3, 6, 9, 12, 18, and 24 months.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Patient must have a histologically confirmed diagnosis of small-cell lung cancer
                   (SCLC)
      
                -  Patient must have an MRI of the brain performed within 28 days prior to registration
                   documenting no evidence of brain metastases or leptomeningeal disease. Patient also
                   must not have a history of brain metastases or leptomeningeal disease
      
                -  Immunotherapy concurrent with and/or adjuvant to first-line therapy is allowed at the
                   discretion of the treating physician. Patients with limited-stage (LS)-SCLC must have
                   completed platinum-based chemotherapy and either definitive thoracic radiotherapy
                   (including stereotactic body radiation therapy [SBRT] for early-stage T1-2 N0 M0
                   disease who do not undergo surgery) or definitive surgical resection; thoracic
                   radiation in addition to definitive surgical resection is allowed at the discretion of
                   the treating physician, but is not required. Patients with extensive-stage (ES)-SCLC
                   must have completed platinum-based chemotherapy either with or without thoracic
                   radiotherapy at the discretion of the treating physician
      
                -  All adverse events from prior treatment must have resolved to =< grade 2 (Common
                   Terminology Criteria for Adverse Events [CTCAE] version 5.0) prior to randomization
      
                -  Patient must have had a response to first-line therapy and no evidence of progression
                   in opinion of the treating investigator. Systemic imaging (computed tomography [CT] or
                   positron emission tomography [PET]/CT including the chest and abdomen) must be
                   performed within 28 days prior to randomization
      
                -  No more than 8 weeks may have elapsed between day 1 of the last cycle of chemotherapy
                   and randomization
      
                -  Patient must not have received prior radiotherapy to the brain or whole brain
                   radiotherapy. Patients who have undergone prior stereotactic radiosurgery for benign
                   tumors or conditions (e.g., acoustic neuroma, grade I meningioma, trigeminal
                   neuralgia) may be considered on a case-by-case basis
      
                -  Patient must have Zubrod performance status of 0-2
      
                -  Patient must not have a contraindication to MR imaging, such as implanted metal
                   devices or foreign bodies
      
                -  Patient must not have a contraindication to gadolinium contrast administration during
                   MR imaging, such as allergy or insufficient renal function
      
                -  Patient must not have other metastatic malignancies requiring current active treatment
      
                -  Patient must not have any severe active comorbidities, defined as follows:
      
                     -  Unstable angina and/or congestive heart failure requiring hospitalization within
                        6 months prior to randomization
      
                     -  Transmural myocardial infarction within 6 months prior to randomization
      
                     -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                        of randomization
      
                     -  Chronic obstructive pulmonary disease exacerbation or other acute respiratory
                        illness precluding study therapy at the time of randomization
      
                     -  Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
                        disease
      
                     -  Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter
      
                          -  Note that patients who are HIV positive are eligible, provided they are
                             under treatment with highly active antiretroviral therapy (HAART) and have a
                             CD4 count >= 200 cells/microliter within 16 weeks prior to randomization
      
                          -  Note also that HIV testing is not required for eligibility for this protocol
      
                -  Patient must not be pregnant because of fetal risks from radiation exposure. Men must
                   have agreed to use an effective contraceptive method during PCI and for six months
                   after completing PCI. Women of reproductive potential must have agreed to use an
                   effective contraceptive method during PCI. A woman is considered to be of
                   "reproductive potential" if she has had menses at any time in the preceding 12
                   consecutive months. In addition to routine contraceptive methods, "effective
                   contraception" also includes heterosexual celibacy and surgery intended to prevent
                   pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
                   bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
                   previously celibate patient chooses to become heterosexually active during the time
                   period for use of contraceptive measures outlined in the protocol, he/she is
                   responsible for beginning contraceptive measures
      
                -  Patients who speak and understand English or French must agree to participate in
                   cognitive function testing
      
                -  Patient must be offered the opportunity to have specimens submitted for banking
      
                -  Patients must be informed of the investigational nature of this study and must sign
                   and give written informed consent in accordance with institutional and federal
                   guidelines
      
                -  As a part of the Oncology Patient Enrollment Network (OPEN) randomization process the
                   treating institution?s identity is provided in order to ensure that the current
                   (within 365 days) date of institutional review board approval for this study has been
                   entered in the system
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Overall survival (OS)
      Time Frame:From the date of registration to date of death due to any cause, assessed up to 2 years after randomization
      Safety Issue:
      Description:Will evaluate OS with magnetic resonance imaging (MRI) surveillance alone and MRI surveillance combined with prophylactic cranial irradiation (PCI) for the treatment of small cell lung cancer (SCLC).

      Secondary Outcome Measures

      Measure:Cognitive failure-free survival (CFFS)
      Time Frame:Baseline to first neurocognitive failure CF or death due to any cause, assessed up to 12 months after randomization
      Safety Issue:
      Description:The comparison of CFFS up to 12 months between the arms will be done using a 1-sided 5% level log-rank test.
      Measure:CFFS rate
      Time Frame:Baseline to first neurocognitive failure CF or death due to any cause, assessed at 90, 180, 270, 360, 540, and 720 days after randomization
      Safety Issue:
      Description:There will be a comparison of the CFFS rates between the arms at each of the assessment times and the cumulative incidence of cognitive failure, evaluating death as a competing risk. The CFFS rates at the landmark times will be estimated using the method of Kaplan-Meier and the difference in rates will be evaluated using a 90% confidence interval using Greenwood?s formula.
      Measure:Cumulative incidence of cognitive failure
      Time Frame:Neurocognitive function test will be assessed at 90, 180, 270, 360, 540, and 720 days after randomization
      Safety Issue:
      Description:The cumulative incidence of cognitive failure in the presence of the competing risk of death will be estimated used the method of Fine and Gray.
      Measure:OS in an "as-treated" analysis
      Time Frame:From the date of registration to date of death due to any cause, assessed up to 2 years after randomization. Patients will be seen at day 90, 180, 270, 360, 540, and 720
      Safety Issue:
      Description:The comparison of OS in the ?as-treated? analysis will be done as described for the primary analysis, however patients will be categorized per treatment received (patients who do not accept their randomized assignment will be analyzed per treatment received). The number of patients not accepting the randomized assignment will also be summarized.
      Measure:Brain metastases-free survival (BMFS)
      Time Frame:Up to 2 years after randomization. Patients will have MRI on day 90, 180, 270, 360, 540, and 720
      Safety Issue:
      Description:This will be estimated using the method of Kaplan-Meier and comparisons will be done using a log-rank test at the 1-sided 0.05 level. Hazard ratios and associated confidence intervals will be estimated using a Cox Proportional hazards model. Confidence intervals for medians will be estimated using the method of Brookmeyer-Crowley.
      Measure:Incidence of adverse events
      Time Frame:Up to 2 years after randomization. Patients will be assessed for adverse event after PCI (for patients on PCI + MRI arm) and at month 3 (all patients)
      Safety Issue:
      Description:Binary proportions and associated confidence intervals will be estimated.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Southwest Oncology Group

      Last Updated

      August 11, 2020