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)

Sponsor

Cardiff University (Other)

Overall Status

Completed

CT.gov ID

NCT01089088

Collaborator

(none)

Enrollment

Locations

Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer	Drug: cisplatin Drug: gemcitabine hydrochloride Drug: sunitinib malate	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Outcome Measures

Primary Outcome Measures

Progression-free survival [6 months]
Proportion of patients progression free at 6 months

Secondary Outcome Measures

Toxicity during and after treatment according to NCI CTCAE v 3.0 [1 Year]
Tolerability (side effects) and feasibility of use (number of patients requiring dose delays or reduction and/or treatment withdrawal) [1 year]
Overall survival [3 years]
Progression-free survival (time-to-event) [1 year]
Objective (radiological) response rate according to RECIST [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bristol Haematology and Oncology Centre	Bristol	Avon	United Kingdom	BS2 8ED
2	Castle Hill Hospital	Cottingham	East Yorkshire	United Kingdom	HU16 5JQ
3	Royal Bournemouth Hospital	Bournemouth	England	United Kingdom	BH7 7DW
4	Churchill Hospital	Oxford	Oxfordshire	United Kingdom	OX3 7LJ
5	Royal Shrewsbury Hospital	Shrewsbury	Shropshire	United Kingdom	SY3 8XQ
6	The Royal Marsden Hospitals (Surrey)	Sutton	Surrey	United Kingdom	Surrey
7	St James's University Hospital	Leeds	Yorkshire	United Kingdom	LS9 7TF
8	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
9	Velindre Hospital	Cardiff		United Kingdom	CF14 2TL
10	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
11	St Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
12	Hammersmith Hospital	London		United Kingdom	W12 0HS
13	St Mary's Hospital (Paddington)	London		United Kingdom	W2 1NY
14	Charing Cross Hospital	London		United Kingdom	W6 8RF
15	Christie Hospital	Manchester		United Kingdom	M20 4BX
16	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD