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Trial record 2 of 30106 for:    Encephalon

Whole Brain Radiation Therapy Alone vs. Radiosurgery for SCLC Patients With 1-10 Brain Metastases (ENCEPHALON)

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ClinicalTrials.gov Identifier: NCT03297788
Recruitment Status : Recruiting
First Posted : September 29, 2017
Last Update Posted : March 5, 2018
Sponsor:
Collaborator:
Heidelberg University
Information provided by (Responsible Party):
Juergen Debus, University Hospital Heidelberg

Brief Summary:

Patients suffering from small cell lung cancer (SCLC) are at high risk for developing brain metastases (BM). To prevent a clinical manifestation of preexisting microscopic brain dissemination, prophylactic cranial irradiation (PCI) is offered to both limited and extensive disease patients, if they respond to first line regime, thus being at risk or at chance to develop clinical brain metastases. However, up to 10-15% of patients present with BM at initial diagnosis. If MRI is used as a diagnostic tool for initial staging the number even increases up to 15-20%. Additionally, between 40 - 50% of patients develop BM until time of death and the risk of developing BM further increases with prolonged survival. Treatment options are usually limited to WBRT and palliative chemotherapy but the actual effect of therapeutic WBRT has mainly been studied in small retrospective and nonrandomized studies. WBRT has been established as the treatment standard in patients with cerebral metastases from SCLC, however, it has only modest efficacy. Results might be improved by additional dose escalation. A SRS to cerebral metastases may be indicated in patients with intracranial disease, and the current protocol is aimed at exploring the neurocognition and efficacy of SCLC in patients with brain metastases treated with SRS or WBRT.

The present trial aims to exploratory investigate the treatment response to ´conventional whole brain radiotherapy´ (WBRT) and ´stereotactic radiotherapy´(SRS) in SCLC patients.


Condition or disease Intervention/treatment Phase
SCLC Brain Metastases Radiation: SRS Radiation: WBRT Phase 2

Detailed Description:

Scientific Background: Patients suffering from BM from SCLC have a poor prognosis with a median survival ranging between 2-14 months. Treatment options for BM in SCLC are usually limited to WBRT, steroids or palliative chemotherapy. SCLC patients demonstrate an exception in the treatment of BM, because treatment options for a limited number of BM from other solid tumors commonly include surgery or SRS with or without WBRT. Even though SCLC is a radiosensitive tumor, higher doses are commonly not applied. Locally ablative treatments like SRS or surgery are less frequently used in patients with BM from SCLC as compared to other types of cancer due to the high incidence of brain metastases in SCLC and the increased likelihood of a diffuse failure pattern. It is of general belief that BM from SCLC are rarely solitary and usually occur at multiple sites. The investigators could not confirm these findings from this analysis as they found 1-5 BM in 39 % of their patients. WBRT, with a treatment time of about two weeks, is commonly the technique of choice for SCLC patients with any number of BM. In a recent Japanese trial, prophylactic cranial irradiation did not result in longer overall survival compared with observation in patients with early disease (ED) SCLC. PCI is therefore no longer recommended for patients with ED SCLC when patients receive regularly MRI examinations during follow-up.

Though, the initial response to cranial irradiation is good, especially in the synchronous setting, SCLC patients are at high risk of developing intracranial recurrence. In the investigators´ retrospective analysis median Overall survival (OS) after re-WBRT was only 2 months and the median OS after SRS was 6 months. These results are similar as compared to results for re-irradiation after PCI. In a recent analysis the investigators reported a prolonged survival for patients treated with SRS in the recurrent setting after previous PCI with a median survival of 5 months.

Therefore, the number of patients with oligometastatic cerebral disease might rise. Based on recursive partitioning Analysis (RPA) classification, the investigators found a median survival after WBRT of 17 months in RPA class I, 7 months in class II and 3 months in class III (p<0.0001), which is comparable to previous analyses using graded prognostic assessment (GPA) scoring. This is further of special interest as patients in RPA class I had a comparable or even better outcome than patients with non-cerebral disease treated with PCI. On the other hand, patients with RPA class III should be carefully selected for WBRT and treatment should be weighed against supportive therapy with steroids alone. This implicates that patient selection is mandatory, even in SCLC, and that the general paradigm of WBRT needs to be reevaluated.

Trial Objectives: The purpose of this trial is to explore the neurocognitive response in patients with brain metastases from SCLC treated with WBRT or SRS. The investigators proposed that patients treated with SRS would have inferior neurocognitive function based on the Hopkins Verbal Learning Test-Revised (HVLT-R) compared with patients treated with SRS alone.

Patients Selection: Patients with a diagnosis of brain metastases from SCLC will be evaluated and screened based on the protocol. All patients fulfilling the inclusion and exclusion criteria will be informed about the possibility to participate in the study. Registration for the study must be performed prior to beginning of RT. 56 patients will be enrolled in this exploratory clinical trial.

Trial Design: This pilot trial will be conducted as a single-center prospective, randomized, two-arm Phase II study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Whole Brain Radiation Therapy (WBRT) Alone Versus Radiosurgery (SRS) for Patients With 1-10 Brain Metastases From Small Cell Lung Cancer
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: SRS
Patient receive stereotactic radiosurgery (SRS), dose prescription according to the size of radiated brain metastases
Radiation: SRS

For SRS the dose prescription to the PTV will be as follows:

  • 20 Gy to the 70%-isodose (lesions < 2 cm max. diameter)
  • 18 Gy to the 70%-isodose (lesions 2 - 3 cm max. diameter)
  • 6 x 5 Gy to the conformally surrounding isodose (lesions > 3 cm max. diameter)

Active Comparator: Arm B: WBRT
Patients receive whole brain radiotherapy (WBRT)
Radiation: WBRT
WBRT will be applied in 10 fractions with single doses of 3 Gy to the whole brain.




Primary Outcome Measures :
  1. Neurocognition [ Time Frame: 3 month after treatment ]
    Drop of at least 5 Points from baseline in HVLT-R test (Hopkins Verbal Learning Test-Revised)


Secondary Outcome Measures :
  1. Intracranial progression [ Time Frame: up to 12 month after treatment ]
    number of new cerebral metastases

  2. Intracranial progression [ Time Frame: up to 12 month after treatment ]
    Change in tumor size

  3. Overall survival (OS) [ Time Frame: 12 month OS ]
    Duration of survival defined as the interval between the date of RT begin and the date of death or date of leaving the study e.g., lost to follow up) whatever occurs first.

  4. Death due to brain metastases [ Time Frame: up to 12 month after treatment ]
    Death which directly connects to existing brain metastases

  5. Locally progression-free survival [ Time Frame: up to 12 month after treatment ]
    12 month Progression-fee survival referring to local tumour progression

  6. Progression-free survival (PFS) [ Time Frame: 12 month PFS ]
    12 month Progression-free survival

  7. Changes in other cognitive performance measures [ Time Frame: up to 12 month after treatment ]
    HVLT_R

  8. Quality of life [ Time Frame: up to 12 month after treatment ]
    BN20 QoL Questionaire

  9. Quality of life [ Time Frame: up to 12 month after treatment ]
    EORTC QoL Questionaire PAL (palliative)

  10. Changes in other cognitive performance measures [ Time Frame: up to 12 month after treatment ]
    CANTAB Test



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:

  • histologically confirmed small cell lung cancer (SCLC)
  • Magentic resonance (MR)-imaging confirmed cerebral metastases (no resection, max. number of 10)
  • age ≥ 18 years of Age
  • For women with childbearing potential, (and men) adequate contraception.
  • Ability of subject to understand character and individual consequences of the clinical trial
  • Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

refusal of the patients to take part in the study

  • previous radiotherapy of the brain
  • Patients who have not yet recovered from acute high-grade toxicities of prior therapies
  • Known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
  • Pregnant or lactating women
  • Participation in another competing clinical study or observation period of competing trials, respectively
  • MRI contraindication (i.e. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements, certain metal implants)
  • Karnofsky score (KPS) <60
  • Simultaneous cytotoxic chemotherapy
  • Last application of chemotherapy/immunotherapy/targeted therapy <1 week before cerebral radiotherapy

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): NCT03297788


Contacts
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Contact: Stefan Rieken, PD. Dr. +49 6221 56 ext 8200 stefan.rieken@med.uni-heidelberg.de
Contact: Denise Bernhardt, Dr. +49 6221 56 ext 8200 denise.bernhardt@med.uni-heidelberg.de

Locations
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Germany
University Hospital of Heidelberg, Department of Radiation Oncology Recruiting
Heidelberg, Germany, 69120
Contact: Juergen Debus, Prof. Dr.Dr.    +49 6221 56 ext 8200    juergen.debus@med.uni-heidelberg.de   
Sub-Investigator: Rami El Shafie, Dr.         
Sub-Investigator: Angela Paul, Dr.         
Sponsors and Collaborators
Juergen Debus
Heidelberg University
Investigators
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Principal Investigator: Stefan Rieken, PD.Dr. chief senior physician in the department of Radiation Oncology

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Juergen Debus, Director of the Department Radiation Oncology, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT03297788     History of Changes
Other Study ID Numbers: S-470/2017
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juergen Debus, University Hospital Heidelberg:
SCLC
Brain Metastases
SRS (stereotactic radiosurgery)
WBRT (whole brain radiotherapy)

Additional relevant MeSH terms:
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Brain Neoplasms
Brain Diseases
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases