Clinical Trial Details
— Status: Suspended
Administrative data
| NCT number |
NCT04084431 |
| Other study ID # |
RECARE Trial Version 1.1 |
| Secondary ID |
|
| Status |
Suspended |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2019 |
| Est. completion date |
July 1, 2025 |
Study information
| Verified date |
January 2024 |
| Source |
University Hospital Heidelberg |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Patients with solid cancers may develop cerebral metastases, requiring whole brain
radiotherapy (WBRT). Furthermore, in several cases, a secondary course of WBRT might be
required due to intracerebral recurrence and limited options for alternative treatments,
besides optimal supportive care (OSC). There have been few reports on re-irradiation of the
whole brain, but further evaluation especially of the optimal dose concept is warranted.
Especially, the efficacy compared to OSC has to date not been evaluated.
The present trial aims at evaluating the efficacy of a repeated WBRT with a total dose of 20
Gy in 10 fractions compared to OSC.
Primary endpoint is time to WHO performance status (PS) deterioration to more than 3
(duration of functional independence).
Secondary endpoints are quality of life, overall survival, radiation-induced toxicity and
functional independence assessed by the Barthel Index of Activities of Daily Living (ADL)1.
Description:
According to Nussbaum et al., 24-45% of cancer patients develop cerebral metastases during
their disease. Brain metastases are generally associated with a poor prognosis and high
morbidity2. Published median survival rates after WBRT are between 2 and 7 months3. Standard
of care in multiple BM is WBRT delivered as total dose of 30 Gy in 10 fractions, leading to
modest palliation with a median survival of 3 to 5 months 4-6. Prognostic factors include the
RPA-classification, performance status, response to steroids and evidence of systemic
disease3,6.
Unfortunately, intracerebral recurrence happens 7-9. For example, in the cohort of Meyners et
al. (2010) on WBRT in relatively radio-resistant tumours, median time to recurrence was 4.5
months and the local control rates at 6 and 12 months after radiotherapy were 37% and 15%,
respectively10. Furthermore, the treatment of intracerebral recurrence after previous WBRT is
challenging. In case of ≤ 3 recurrent BM, surgery or stereotactic radiosurgery (SRS) are
options. One other option, especially in case of >3 recurrent BM is repeated WBRT. In this
setting, one of the first reports on repeated WBRT was published by Cooper et al. in 199011.
The authors reported on repeated WBRT (n=52) consisting of a total dose of 25 Gy in 10
fractions. Response to re-irradiation was seen in about 40% of the patients. Furthermore, the
patients improved by at least one level in their neurologic function status. Survival after
second therapy averaged 5 months. In the report by Wong et al. (1996) median dose of
retreatment (n=86) was 20 Gy12. Resolution of symptoms was achieved in 27% of patients,
partial improvement in 43% and no improvement or worsening of symptoms was seen in 29% of
patients. The majority of patients had no significant toxicity in consequence of
re-irradiation. Five patients had radiographic abnormalities of their brain consistent with
radiation-related changes. One patient had symptoms of dementia that was thought to be caused
by radiotherapy. Sadikov et al. (2007) reported on 72 patients who underwent repeated WBRT
for recurrent or progressive BM13. The median survival after re-irradiation was 4.1 months.
One patient was reported having memory impairment and pituitary insufficiency after 5 months
of progression-free survival.
In the report by Mayer et al. on re-irradiation tolerance of the human brain (this analysis
was focused on recurrent glioma), the authors concluded that radiation-induced brain tissue
necrosis is likely to occur at normalized tolerance doses of cumulative > 100 Gy14.
The recent QUARTZ trial investigated the efficacy of WBRT vs. OSC in patients with non-small
cell lung cancer and low performance status. The results suggest that WBRT, even in the
primary situation, offers no substantial benefit to most patients with brain metastases from
NSCLC in terms of improved survival, overall quality of life, or reduction of steroid use in
this cohort15.
In the present trial, the primary endpoint (time to WHO PS deterioration to more than 3) as
well as the secondary endpoints QoL, overall survival, radiation-induced toxicity and
functional independence assessed by the Barthel Index of Activities of Daily Living (ADL) in
patients previously treated with WBRT requiring repeated WBRT for intracerebral tumour
progression will be evaluated.
