JOURNAL ONKOLOGIE – STUDIE
ENCEPHALON Whole Brain Radiation Therapy Alone vs. Radiosurgery for SCLC Patients With 1-10 Brain Metastases
Rekrutierend
NCT-Nummer:
NCT03297788
Studienbeginn:
Dezember 2017
Letztes Update:
11.09.2020
Wirkstoff:
-
Indikation (Clinical Trials):
Neoplasm Metastasis, Neoplasms, Second Primary, Brain Neoplasms
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 2
Sponsor:
Juergen Debus
Collaborator:
Heidelberg University
Studienleiter
Principal Investigator
chief senior physician in the department of Radiation Oncology
Kontakt
Kontakt:
Phone: +49 6221 56
Phone (ext.): 8200
E-Mail: stefan.rieken@med.uni-heidelberg.de» Kontaktdaten anzeigen
Kontakt:
Phone: +49 6221 56
Phone (ext.): 8200
E-Mail: denise.bernhardt@med.uni-heidelberg.de» Kontaktdaten anzeigen
Studienlocations (1 von 1)
University Hospital of Heidelberg, Department of Radiation Oncology
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Juergen Debus, Prof. Dr.Dr.
Phone: +49 6221 56
Phone (ext.): 8200
E-Mail: juergen.debus@med.uni-heidelberg.de» Ansprechpartner anzeigen
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Juergen Debus, Prof. Dr.Dr.
Phone: +49 6221 56
Phone (ext.): 8200
E-Mail: juergen.debus@med.uni-heidelberg.de» Ansprechpartner anzeigen
Studien-Informationen
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.
Ein-/Ausschlusskriterien
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
Studien-Rationale
Primary outcome: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:
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
Studien-Arme
- Experimental: Arm A: SRS
Patient receive stereotactic radiosurgery (SRS), dose prescription according to the size of radiated brain metastases - Active Comparator: Arm B: WBRT
Patients receive whole brain radiotherapy (WBRT)
Geprüfte Regime
- 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) - WBRT:
WBRT will be applied in 10 fractions with single doses of 3 Gy to the whole brain.
Quelle: ClinicalTrials.gov
