Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02394626 |
| Other study ID # |
368/14 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2015 |
| Est. completion date |
December 2025 |
Study information
| Verified date |
July 2023 |
| Source |
Insel Gruppe AG, University Hospital Bern |
| Contact |
Luisa Neves da Silva |
| Phone |
+41 31 66 4 28 65 |
| Email |
luisa.nevesdasilva[@]insel.ch |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Patients with glioblastoma face a grim prognosis. Despite recent advancement in neurosurgical
technology and neuro-oncology glioblastomas almost invariably progress or recur after a
median of 4-8 months. The strategy to repeat tumor resection at recurrence in order to
minimize tumor load and thus to facilitate subsequent second-line therapy has been shown to
be feasible and safe.
However, evidence for a survival benefit of surgery for recurrent glioblastoma is scarce and
relies entirely on retrospective analyses. While most retrospective analyses report an
apparent survival benefit, an EORTC meta-analysis on second-line therapies found no survival
difference in patients with or without surgery at recurrence. With regard to the risks and
costs inherent to surgery for glioblastoma, a randomized controlled trial is required.
The purpose of the study is to compare the effect of craniotomy and tumor resection followed
by adjuvant second-line therapy to no surgery followed by second-line therapy on overall
survival, neurological status, and quality of life. Analysis of overall survival will be used
to improve sample size estimation of a subsequent phase III trial for craniotomy and tumor
resection of glioblastoma recurrence in cooperation with the EORTC.
Description:
Background
Glioblastoma is a malignant, locally invasive brain tumor whose prognosis remains grim
despite various intense treatment modalities. In the past, radical surgery was met with
skepticism due to the aggressive infiltrative character of the tumor. However, an increasing
number of retrospective studies over the last decade suggest a survival benefit for surgery.
A recent post-hoc analysis of a randomized controlled trial on the use of the surgical
adjunct 5-ALA reported a prolonged overall survival from 11.9 to 16.7 months (evidence level
2a) after more extensive resection. Thus, maximal safe resection has become a mainstay of
treatment for newly diagnosed glioblastoma, followed by adjuvant radio-chemotherapy.
Glioblastoma almost invariably recurs after a median of 6.9 months, leaving but few options
for further treatment. Recurrence of glioblastoma after surgery and concomitant adjuvant
therapy represents an additional therapeutic challenge and may be treated with second-line
pharmacotherapy. In addition, a second surgery may also be considered in highly selected
patients.
The rationale for surgery - maximum safe resection - is to prolong survival through reduction
of tumor load, and, maybe due to an increased efficacy of adjuvant treatment. However,
surgery carries risks of complications, that may result in a decreased functional and
survival outcome. The crucial question therefore is whether, to what extent, and at what
costs in terms of neurological risks a second resection prolongs survival.
Objective
The primary objective of this randomized trial is to compare survival outcome after surgery
followed by adjuvant second-line therapy to no surgery followed by second-line therapy in
recurrent glioblastoma. An auxiliary objective to primary objective is to compare the
survival outcomes of operated patients to control in the subgroups stratified by extent of
resection: incomplete resection (non-CRET) vs complete resection (CRET).
Secondary objectives are: assessment of recruitment for all screened patients, comparison of
progression-free survival between treatment arms, evaluation of crossover and comparison of
patient quality of life between treatment arms.
Safety objectives are: to assess neurological deficits, local infections and morbidity
associated to surgery and hospital stay after surgery and during follow-up.
Methods
All patients (≥18 years) with a radiological suspicion of first recurrence of glioblastoma
are screened for this trial. Patients eligible for study participation are informed on the
treatment options for recurrent glioblastoma (surgery followed by adjuvant second-line
therapy, second-line therapy, or palliative therapy alone) by the center investigators.
Patients randomized to the control group will receive second-line therapy according to local
guidelines. Patients randomized to the interventional group will receive a craniotomy and
resection of the tumor followed by adjuvant second-line therapy. Outcome will be measured at
3 months intervals.
Recruitment rate and reason for non-inclusion will be monitored.
