Clinical trial NCT02951325: Bladder Cancer Adjuvant Radiotherapy Trial
Official title: Prospective Randomized Trial of Adjuvant Radiotherapy Following Surgery and Chemotherapy in Muscle Invasive Transitional Cell Carcinoma of Urinary Bladder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Bladder Cancer
Urothelial Carcinoma Bladder
Keywords: adjuvant RT
Lead sponsor: Tata Memorial Centre
Sponsor class: OTHER
First posted: 2016-11-01
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Aim and objectives:

This trial aims to evaluate the role of adjuvant radiotherapy following chemotherapy in patients with high-risk features on histo-pathology after radical surgery for transitional cell carcinoma of urinary bladder

Detailed description: Treatment details:

Surgery(Standard/routine care) All patients would have undergone radical surgery in the form of a cysto-prostatectomy and pelvic nodal dissection as part of their standard care. Patients would also have a urinary diversion (Ileostomy) or a continent neo bladder.

Chemotherapy All patients following cysto-prostatectomy will receive upto 4 cycles of adjuvant chemotherapy if medically fit for the same. Those patients who received neoadjuvant chemotherapy, will receive additional chemotherapy cycle after surgery to a total of 4 cycles if found suitable. The chemotherapy regimen, doses and schedule will be as per standard institutional practice using Platinum based chemotherapy. No concomitant chemotherapy with radiotherapy is recommended.

Radiation therapy:

All patients will be treated with conformal radiotherapy technique with intensity modulated radiotherapy with or without image guidance. The radiotherapy will start within maximum of 8 weeks from the date of surgery if adjuvant chemotherapy has not been planned. If adjuvant chemo planned the patients will receive radiotherapy within 4 weeks of the last chemo cycle.

Dose Prescription:

50.4Gray (Gy) in 28fractions (1.8Gy/#) will be prescribed for the nodal PTV. In case of R1 and/or R2 resection dose to the pelvic nodes and tumour bed may be increased to 54-56Gy in 28 fractions depending on the constraints achieved during planning.

Clinical assessment:

1. Toxicity will be assessed by

   1. Weekly physician assessment during RT with scoring of toxicity.
   2. RTOG toxicity criteria at baseline, 6-8 weeks post RT and at 3 monthly thereafter for 2 years and 6 monthly thereafter for 5 years.
   3. QOL will be assessed at baseline and 3-6 monthly thereafter
2. Disease evaluation The first follow up all patients will be done at 6-8 week to assess toxicity. Clinical evaluation of the disease will be done at each follow up visits by clinical examination. CT scan of the abdomen and pelvis will be done 6 monthly from second visit onwards up to 2 years and 12 monthly thereafter or whenever clinically indicated as decided by the physician.

Eligibility criteria: Inclusion Criteria:

All patients should have undergone radical cystoprostatectomy for bladder cancer Patients with any of the below high risk features on histolopathology

* Lymph Node positive with or without perinodal extension (PNE)
* Cut-margin positive,
* pT3 and pT4 disease,
* Number of nodes dissected at surgery \< 10 All patients irrespective of the final pathology if they have received neo-adjuvant chemotherapy prior to surgery for any of the following T3 T4 stage N1-3 stage No evidence of distant metastasis including para-aortic nodal metastasis KPS ≥ 70 Signed study specific consent form Adequate hepatic, renal and hematologic parameters

Exclusion Criteria:

* Contraindication to pelvic radiotherapy like inflammatory bowel disease
* Uncontrolled diabetes or hypertension
* Uncontrolled cardiac or respiratory co morbidity
* Prior history of therapeutic irradiation to pelvis
* Patient unwilling and unreliable for follow up and QoL

Primary outcomes:
measure: Improvement in loco-regional relapse free survival (LRFS)
timeFrame: 2 year
Secondary outcomes:
measure: Disease free survival (DFS)
timeFrame: two and five years
measure: Overall survival(OS)
timeFrame: two and five years
measure: RT toxicity (acute and late)
timeFrame: 6 months and 2 years
measure: QOL
timeFrame: 2 years
measure: Patterns of failure
timeFrame: 2 years
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Tata Memorial Centre
state: Maharashtra
Study officials:
References:
citation: Murthy V, Maitre P, Singh M, Pal M, Arora A, Pujari L, Kapoor A, Pandey H, Sharma R, Gudipudi D, Joshi A, Prabhash K, Noronha V, Menon S, Mehta P, Bakshi G, Prakash G. Study Protocol of the Bladder Adjuvant RadioTherapy (BART) Trial: A Randomised Phase III Trial of Adjuvant Radiotherapy Following Cystectomy in Bladder Cancer. Clin Oncol (R Coll Radiol). 2023 Sep;35(9):e506-e515. doi: 10.1016/j.clon.2023.04.010. Epub 2023 May 5.
citation: Murthy V, Maitre P, Bakshi G, Pal M, Singh M, Sharma R, Gudipudi D, Pujari L, Pandey H, Bandekar B, Joseph D, Krishnatry R, Phurailatpam R, Kannan S, Arora A, Misra A, Joshi A, Noronha V, Prabhash K, Menon S, Prakash G. Bladder Adjuvant Radiation Therapy (BART): Acute and Late Toxicity From a Phase III Multicenter Randomized Controlled Trial. Int J Radiat Oncol Biol Phys. 2025 Mar 1;121(3):728-736. doi: 10.1016/j.ijrobp.2024.09.040. Epub 2024 Sep 29.