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Trial record 1 of 1 for:    CC003
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Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Treating Patients With Limited Stage or Extensive Stage Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02635009
Recruitment Status : Recruiting
First Posted : December 18, 2015
Last Update Posted : May 11, 2022
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
NRG Oncology

Study Description
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Brief Summary:
This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.

Condition or disease Intervention/treatment Phase
Extensive Stage Small Cell Lung Carcinoma Limited Stage Small Cell Lung Carcinoma Radiation: 3-Dimensional Conformal Radiation Therapy Other: Cognitive Assessment Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Phase 2 Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 392 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer
Study Start Date : December 2015
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm I (PCI using 3DCRT)
Patients undergo PCI using 3DCRT daily for 2 weeks.
 Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo PCI using 3DCRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy

Other: Cognitive Assessment
Ancillary studies

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm II (PCI with HA using IMRT)
Patients undergo PCI with HA using IMRT daily for 2 weeks.
 Other: Cognitive Assessment
Ancillary studies

Radiation: Intensity-Modulated Radiation Therapy
Undergo PCI with HA using IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment


Outcome Measures
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Primary Outcome Measures :
  1. HVLT-R delayed recall deterioration status, defined using the Reliable Change Index (RCI) (Phase III) [ Time Frame: 6 months from start of treatment ]
    Compared using Fisher's exact test at a significance level of 0.05.

  2. Intracranial relapse rate (Phase II) [ Time Frame: 12 months ]
    It will be compared between arms using a binomial test of difference in proportions at a significance level of 0.1. If the rate of relapse in the HA-PCI arm is significantly greater than that of the PCI only arm, this study will not continue to the phase III portion.


Secondary Outcome Measures :
  1. Cost-effectiveness as measured by the EQ-5D (Phase III) [ Time Frame: Up to 3 years ]
    Quality-adjusted life years (QALY's) will be assessed as the area under the preference-weighted survival curve. Cost will be assessed using a societal perspective. The primary cost-effectiveness outcome will be the pooled incremental cost-per QALY ratio for HA-PCI versus standard PCI. The incremental cost per QALY ratio will be calculated as the total cost of the HA-PCI minus total cost of standard PCI which will be divided by the quality adjusted survival of the patients treated with HA-PCI minus the quality adjusted survival of patients receiving standard PCI.

  2. Incidence of adverse events (AEs), as measured by the CTCAE v.4 (Phase III) [ Time Frame: Up to 3 years ]
    Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm.

  3. Intracranial relapse rate (Phase III) [ Time Frame: Up to 12 months ]
    The occurrence of intracranial relapse will be defined as appearance of brain metastasis in brain. Cumulative incidence approach will be used to estimate the median time to intracranial relapse to account for the competing risk of death. Gray's test will be used to test for statistically significant difference in the distribution of intracranial relapse times. Cause-specific Cox proportional hazards regression model will be used to evaluate effect of stratification variables (age, stage, and planned concurrent memantine use) and other baseline characteristics, on time to intracranial relapse.

  4. Overall survival (Phase III) [ Time Frame: From the date of randomization to the date of death, or, otherwise, the last follow-up date on which the patient was reported alive, assessed up to 3 years ]
    Estimated using the Kaplan-Meier method and differences between treatment arms will be tested using the log rank test. The Cox proportional hazard model will be performed with the stratification variables and other baseline characteristics as fixed variables to assess the treatment effect while adjusting for patient-specific risk factors.

  5. Patient-reported HRQOL, as measured by the EORTC QLQ-C30 and BN20 (Phase III) [ Time Frame: Up to 24 months ]
    Correlation of changes in HRQOL domains measured by the EORTC QLQ-C30 and BN20 with changes in cognitive function will be assessed. Additionally cognitive function decline at 3, 6, 12, 18 and 24 months will also be assessed and compared using Fisher's exact test. Decline from baseline to each time point (3, 6, 12, 18, and 24 months from the start of treatment) in the following subscales will also be assessed and compared using Fisher's exact test: global QOL, physical functioning, role functioning, emotional functioning, and social functioning domains along with fatigue and pain items.

  6. Preservation of neurocognitive function, as measured by neurocognitive decline for HVLT-R, COWA test, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP) score (Phase III) [ Time Frame: Up to 24 months ]
    Standardized scores that adjust for age, education, and gender when necessary will be analyzed. For discrete time point analyses, the change from baseline to each follow-up time point (3, 6, 12, 18, and 24 months from the start of treatment) will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann- Whitney test, depending on the normality of the data. Neurocognitive decline using the RCI for the HVLT-R, COWA, and TMT also will be compared between treatment arms at each follow-up time point using Fisher's exact test.

  7. Time to neurocognitive failure, where a failure is defined using the RCI criteria, as measured by HVLT-R, COWA test, and TMT Parts A and B (Phase III) [ Time Frame: Up to 3 years ]
    The cumulative incidence approach will be used to estimate the median time to neurocognitive failure to account for the competing risk of death. Gray's test will be used to test for statistically significant difference in the distribution of neurocognitive failure times. The cause-specific Cox proportional hazards regression model will be used to evaluate the effect of stratification variables (age, stage, and planned concurrent memantine use) and other baseline characteristics, on time to neurocognitive decline.


Other Outcome Measures:
  1. White matter injury and hippocampal volume on neurocognitive function [ Time Frame: Baseline to 6 months ]
    The change from baseline to 6 months will be compared between arms using the t-test (or Wilcoxon test if not normally distributed) in the total score and the two subscale scores (agency and pathway). These scores will be correlated with the EORTC- QLQ-C30 total score using a Pearson correlation coefficient. A general linear model will be used to assess hopefulness, performed separately for the AHS total score and subscale scores, between treatment arms while adjusting for depression.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION

  • Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration

    • High-grade neuroendocrine carcinoma or combined SCLC and NSCLC is permitted.

  • Patients must have received chemotherapy and be registered to Step 1 registration no earlier than 7 days and no later than 56 days after completing chemotherapy. Note:

    • Post-chemotherapy restaging imaging must be completed no more than 56 days prior to Step 1 registration.
    • For patients with extensive-stage small cell lung cancer who are being considered for consolidative thoracic radiotherapy after chemotherapy, concomitant administration of consolidative thoracic radiotherapy and protocol-specified prophylactic cranial irradiation with or without hippocampal avoidance is permitted.

  • Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan (see section 11.3 regarding axial T2/FLAIR sequence). To yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan must use the smallest possible axial slice thickness not exceeding 1.5 mm. Sites may contact the Imaging Co-Chairs for further information or assistance if needed.

    • This MRI must be obtained within 56 days prior to Step 1 registration. Note: The MRI study is mandatory irrespective of randomization to the experimental or control arm of this study.

  • Prior to chemotherapy +/- thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following:

    1. History/physical examination;
    2. CT of the chest and abdomen with contrast (does not have to be done if the patient has had a PET/CT scan prior to initiating chemotherapy or thoracic radiotherapy);
    3. MRI of the brain with contrast or diagnostic head CT with contrast;
    4. For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI or head CT, a PET/CT or bone scan is required to confirm limited-stage SCLC.

  • After chemotherapy, patients must be restaged prior to Step 1 registration using the same diagnostic work-up as required pre-chemotherapy. Repeat PET/CT or bone scan is not required. Patients must have:

    • History/physical examination within 30 days of Step 1 registration;
    • No CNS metastases (Repeat MRI required; see Section 3.2.3 for details) within 56 days prior to Step 1 registration;
    • No progression in any site;

    • Radiographic partial or complete response to chemotherapy in at least one disease site within 56 days prior to Step 1 registration.

      1. If PET/CT was obtained prior to chemotherapy, either a repeat PET/CT or CT of the chest and abdomen with contrast can be obtained for response assessment.
      2. Patients who underwent resection for limited-stage SCLC prior to chemotherapy and have no radiographically evident disease for response assessment remain eligible if post-chemotherapy imaging demonstrates no progression.
  • Zubrod performance status 0-2
  • Women of childbearing potential and male participants must practice adequate contraception
  • Women of childbearing potential must have a negative qualitative serum pregnancy test =< 2 weeks prior to study entry
  • Patients who are primary English or French speakers are eligible
  • Patients must sign a study-specific informed consent prior to study entry
  • PRIOR TO STEP 2 REGISTRATION
  • The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (Parts A and B), and COWA. The neurocognitive assessments will be uploaded into the NRG Oncology RAVE System for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days, a notification email will be sent to the site to proceed to Step 2 registration. At minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible.
  • Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall

Exclusion Criteria:

  • Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
  • Radiographic evidence of CNS metastases
  • Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt

  • Planned concurrent chemotherapy or anti-tumor agent during PCI

    • Concurrent atezolizumab permitted
  • Concomitant invasive malignancy or invasive malignancy within the past five years other than non-melanomatous skin cancer; history of in situ carcinoma (e.g. ductal carcinoma in situ of breast, in situ carcinoma of the cervix, vulva or larynx) is permitted
  • Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia

  • Severe, active comorbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Uncontrolled, clinically significant cardiac arrhythmias

    • HIV positive with CD4 count < 200 cells/microliter;

      1. Note: 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 30 days prior to Step 1 registration.
      2. Note: HIV testing is not required for eligibility for this protocol.
  • Pregnant or lactating women or women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02635009


Locations
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Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Investigators
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Principal Investigator: Vinai Gondi NRG Oncology
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT02635009    
Other Study ID Numbers: NRG-CC003
NCI-2015-01548 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-CC003 ( Other Identifier: NRG Oncology )
NRG-CC003 ( Other Identifier: DCP )
UG1CA189867 ( U.S. NIH Grant/Contract )
First Posted: December 18, 2015    Key Record Dates
Last Update Posted: May 11, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Small Cell Lung Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
 Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases