- To evaluate the bladder-preservation rate after chemoradiation - To evaluate the toxicity and complications of treatment with induction chemotherapy followed by ePLND and chemoradiation
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Bladder and bladder neck disorders (excl calculi)
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-To evaluate the bladder-preservation rate after chemoradiation
-To evaluate the recurrence of disease after 12 months followup, following
chemoradiation
Secondary outcome
- Recurrence rates (local and distant)
- Toxicity rates following induction chemotherapy
- Complication rates following ePLND
- Toxicity rates following chemoradiation
- Quality of Life (EuroQol EQ-5D-3L; SF-12)
- Disease specific survival
- Recurrence free survival
- Genetic biomarkers
Background summary
Systemic treatment with cisplatin-based combination chemotherapy has been shown
to improve the outcome of patients presenting with locally advanced
muscle-invasive bladder cancer and patients with lymph node positive disease,
albeit at best an absolute 6.5% increase in overall survival at 5-years
follow-up. Aims of the present study are: to evaluate the bladder preservation
rate after chemoradiation, and furthermore assessment of the toxicity and
complications of induction cisplatin-based combination chemotherapy followed by
pelvic lymph node dissection (ePLND) and chemoradiation.
Study objective
- To evaluate the bladder-preservation rate after chemoradiation
- To evaluate the toxicity and complications of treatment with induction
chemotherapy followed by ePLND and chemoradiation
Study design
Prospective single arm, multicenter fase-II trial
Intervention
After initial staging and informed consent, patients will receive induction
chemotherapy followed by ePLND and chemoradiation.
Induction chemotherapy consists primarily of a cisplatin-based regimen, being
either high dose intensity MVAC or gemcitabine with cisplatin (Gem/Cis). In
case of severe toxicity the schedule may be adjusted to a regimen containing
gemcitabine with carboplatin.
Extended pelvic lymph node dissection (ePLND) consists of removal of all
pathological lymph nodes together with standard PLND consisting of the removal
of all nodes in the region between: the genito-femoral nerve, the obturator
fossa, along the internal iliac artery and along the common iliac artery up to
the crossing of the ureter or the bifurcation of the aorta. In supraregional
spread, also a full RPLND is done. Generally, surgery will be performed within
4-6 weeks after the final course of chemotherapy.
The chemoradiation will start 2-6 weeks following ePLND. There is a wide spread
in treatment techniques and availabilities of different techniques among the
different institutions. Each institution is free to choose their own treatment
technique and margins, but has to define beforehand which technique and margins
will be used. The use of adaptive radiotherapy is strongly encouraged but not
mandatory.
In case of a solitary bladder tumor on cystoscopy, the patients will be treated
with radiotherapy to a dose of 45 Gy to the bladder and 60 Gy to the Gross
Tumour volume (GTV), both in 25 fractions. In case of multiple bladder tumors
(>= 2) the whole bladder will be treated to a dose of 60 Gy (whole bladder
irradiation).
Patients will receive concomitant chemotherapy during the radiotherapy
treatment. Capecitabine 750 mg/m2 twice daily on weekdays and Mitomycine (12
mg/m2 intravenous bolus dose on day 1).
Study burden and risks
The complication-risks of the current 'standard-therapy' consisting of
neoadjuvant chemotherapy followed by total cystectomy with urinary diversion
are considerable (35-50%). The current study-protocol will offer patients the
possibility of bladderpreservation and potentially a decreased
complication-risk.
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
All patients with locally advanced (T3-4) and/or node positive bladder cancer (>=N1), who are fit to receive cisplatin-based combination chemotherapy and who are eligible for surgery, may be included in this study. ;Inclusion criteria:
- Signed written informed consent
- Locally advanced urothelial carcinoma of the bladder (cT3-T4) or any cT-stage with cytologically or histologically proven node positive urothelial carcinoma (or positive FDG/PET-CT-scan with suspect lymph nodes, including supraregional retroperitoneal lymph nodes below the diaphragm.
- Renal function: Creatinin clearance >= 50 mL/min (calculated) and serum creatinin <=1.5 x UNL.
- In case of hydronefrosis: relative function of the hydronefrotic kidney should be at least 30%.
- Karnofsky performance >=70
Exclusion criteria
Exclusion criteria:
-Distant metastases (M+)
-Severe bladder symptoms (necessitating cystectomy).
-Bilateral hydronefrosis.
-Persisting hydronephrosis after induction chemotherapy (necessitating cystectomy). A temporary nefrostomy is indicated during chemotherapy.
-Previous radiation therapy on pelvic region
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL51464.031.15 |