Clinical trial NCT01089088: Gemcitabine Hydrochloride, Cisplatin, and Sunitinib Malate as First-Line Therapy in Treating Patients With Locally Advanced And/or Metastatic Transitional Cell Carcinoma of the Urothelium (SUCCINCT)
Official title: A Phase II Single-Arm Trial to Evaluate Cisplatin and Gemcitabine Chemotherapy in Combination With Sunitinib for First-Line Treatment of Patients With Advanced Transitional Carcinoma of the Urothelium
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Keywords: recurrent urethral cancer
recurrent transitional cell cancer of the renal pelvis and ureter
metastatic transitional cell cancer of the renal pelvis and ureter
regional transitional cell cancer of the renal pelvis and ureter
posterior urethral cancer
urethral cancer associated with invasive bladder cancer
transitional cell carcinoma of the bladder
stage IV bladder cancer
recurrent bladder cancer
anterior urethral cancer
Lead sponsor: Cardiff University
Sponsor class: OTHER
First posted: 2010-03-18
Enrollment: 63
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving gemcitabine hydrochloride and cisplatin together with sunitinib malate may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving gemcitabine hydrochloride and cisplatin together with sunitinib malate and to see how well it works as first-line therapy in treating patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium.

Detailed description: OBJECTIVES:

* To determine the activity, safety, and feasibility of gemcitabine hydrochloride and cisplatin in combination with sunitinib malate as first-line therapy in patients with locally advanced and/or metastatic transitional carcinoma of the urothelium.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, cisplatin IV over 3-4 hours on day 1, and oral sunitinib malate once daily on days 2-15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 6 months and 1 year.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed transitional cell carcinoma of the urothelium

  * Pure or mixed histology
  * Upper or lower urinary tract
* Radiologically measurable, locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy meeting 1 of the following criteria:

  * T4b (bladder) or T4 (renal pelvis/ureter), any N, any M
  * Any T, N2-3, any M
  * Any T, any N, M1
* No urothelial cancer for which subsequent radical treatment is being considered with a view to possibly cure the disease
* No history of CNS metastases

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Life expectancy \> 3 months
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT and ALP ≤ 2.5 times ULN
* GFR ≥ 60 mL/min (uncorrected for surface area and measured by isotopic means)
* PT or INR ≤ 1.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Fit to receive cisplatin-containing combination chemotherapy
* No previous malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or incidental localized prostate cancer
* No known HIV positivity or chronic hepatitis B or C infection
* No uncontrolled hypertension
* No symptomatic coronary artery disease, myocardial infarction within the past 6 months, congestive cardiac failure (NYHA class III-IV disease), or uncontrolled or symptomatic cardiac arrhythmia
* No clinically significant bacterial or fungal infection
* No concurrent grapefruit juice

PRIOR CONCURRENT THERAPY:

* At least 1 month since prior radiotherapy or radiotherapy involving more than 30% of total bone marrow volume
* At least 1 month since prior investigational drug
* No prior systemic therapy for locally advanced or metastatic disease

  * Patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to 4 courses), completed at least 6 months prior to first documented disease progression, are eligible
* No concurrent anticoagulant therapy with warfarin or unfractionated heparin

  * Patients requiring anticoagulation may be entered on study after successful conversion to low molecular weight heparin
* No concurrent medications that have known adverse interactions with sunitinib malate (i.e., strong CYP3A4 inhibitors or inducers)
* No prior or concurrent live vaccines (e.g., measles, mumps, rubella, oral polio, bacille Calmette-Guérin \[BCG\], yellow fever, varicella, and TY21a typhoid vaccines)

Primary outcomes:
measure: Progression-free survival
timeFrame: 6 months
Secondary outcomes:
measure: Toxicity during and after treatment according to NCI CTCAE v 3.0
timeFrame: 1 Year
measure: Tolerability (side effects) and feasibility of use (number of patients requiring dose delays or reduction and/or treatment withdrawal)
timeFrame: 1 year
measure: Overall survival
timeFrame: 3 years
measure: Progression-free survival (time-to-event)
timeFrame: 1 year
measure: Objective (radiological) response rate according to RECIST
timeFrame: 1 year
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: Avon
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: East Yorkshire
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: Shropshire
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospitals (Surrey)
state: Surrey
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: Yorkshire
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital (Paddington)
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Royal Bournemouth Hospital
name: Tom Geldart
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chang SS. Re: SUCCINCT: An Open-Label, Single-Arm, Non-Randomised, Phase 2 Trial of Gemcitabine and Cisplatin Chemotherapy in Combination with Sunitinib as First-Line Treatment for Patients with Advanced Urothelial Carcinoma. J Urol. 2015 Dec;194(6):1583-4. doi: 10.1016/j.juro.2015.09.005. Epub 2015 Sep 5. No abstract available.