eoadjuvant Radiotherapy (N-RT) for Intracerebal Metastases of Solid Tumors

Phase 1

Recruiting

Conditions: C79.3
Secondary malignant neoplasm of brain and cerebral meninges

Registration Number: DRKS00016613

Lead Sponsor: Klinik für Radioonkologie, Klinikum rechts der Isar, TU München

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 48

Inclusion Criteria

Patients meeting all of the following criteria will be considered for admission to the trial:
•Patients with 1-4 intracerebral metastases on contrast-enhanced MRI from solid tumors with known histology confirmed
•One brain metastasis is = 3cm in size or
-Persisting neurologic symptoms or symptomatic epilepsy from brain metastases despite treatment with steroids.
-Tumor location close to eloquent brain areas therefore neurological symptoms can be expected without longtime steroidal medication.
-Patient is deciding to undergo surgical intervention, if resection and radiation therapy are equal treatment options or if the patient declines radiation therapy.
•Age = 18 years of age
•Karnofsky Performance Score = 70, ECOG = 1
•For women with childbearing potential 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

Patients presenting with any of the following criteria will not be included in the trial:
•Patients with unknown primary (CUP)
•Tumor diameter of any single lesion exceeding 4 cm
•Tumors causing severe neurological deficits or with mass effect requiring immediate surgical intervention
•Previous radiotherapy to the brain
•Known tumor of small cell histology, germ cell histology or lymphoma
•Refusal of the patients to take part in the study
•Patients who have not yet recovered from acute toxicities of prior therapies
•Clinically active kidney-liver or cardiac disease
•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

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary endpoint is to find the MTD for which no dose limiting toxicities (DLT) occur will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (2017) continuously during the study until first follow up (4-6 weeks after surgery) for each cohort and dose level. A DLT is defined as central nerve system necrosis (=G3) or cerebrospinal fluid leakage (=G4) or wound infection ((=G4) or wound dehiscence (=G4) or postoperative hemorrhage (=G4) or cognitive disturbance (=G4) or cerebral edema (=G4) or headache (=G4) or seizure (=G4).

Secondary Outcome Measures

Name	Time	Method
Secondary endpoints are the following:<br><br>•Central nerve system necrosis according CTCAE Grade 1-3<br>•Cerebrospinal fluid leakage according CTCAE Grade 1-3<br>•Wound infection CTCAE Grade 1-3<br>•Wound dehiscence CTCAE Grade 1-3<br>•Cerebral edema according CTCAE Grade 1-3 <br>•Local control rates <br>•Overall survival and progression free survival at 12 months follow up<br>•Time interval between treatment initiation and start of systemic chemotherapy. <br>•Health-related quality of life using the EuroQol questioner.<br>•Assessment of neurocognitive function applying Minimal Mental State Examination (MMSE) testing.<br>•Late toxicity according CTCAE Grad 1-5<br>•Immunological Parameters (such as PD-L1 expression on the resection specimen)<br>