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)

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01089088
• Other study ID #: CDR0000667764
• Secondary ID: WCTU-SUCCINCTISR
• Status: Completed
• Phase: Phase 2
• Start date: April 2009
• Est. completion date: October 2014

Study information

• Verified date: February 2013
• Source: Cardiff University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 120 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureteral Neoplasms
• Urethral Cancer
• Urethral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin
Up to six 21 day chemotherapy cycles: Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)
• gemcitabine hydrochloride
Up to six 21 day chemotherapy cycles: Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)
• sunitinib malate
Up to six 21 day chemotherapy cycles: Cisplatin 70mg/m2 (IV day 1) Gemcitabine 1000mg/m2 (IV days 1 & 8) Sunitinib 37.5mg (po days 2 to 15)

Locations

Country	Name	City	State
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	Avon
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Velindre Hospital	Cardiff
United Kingdom	Castle Hill Hospital	Cottingham	East Yorkshire
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James's University Hospital	Leeds	Yorkshire
United Kingdom	Charing Cross Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	St Mary's Hospital (Paddington)	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Churchill Hospital	Oxford	Oxfordshire
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	Shropshire
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	The Royal Marsden Hospitals (Surrey)	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Cardiff University

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Proportion of patients progression free at 6 months	6 months
Secondary	Toxicity during and after treatment according to NCI CTCAE v 3.0		1 Year
Secondary	Tolerability (side effects) and feasibility of use (number of patients requiring dose delays or reduction and/or treatment withdrawal)		1 year
Secondary	Overall survival		3 years
Secondary	Progression-free survival (time-to-event)		1 year
Secondary	Objective (radiological) response rate according to RECIST		1 year

External Links

•   Summary on sponsor website
•   Trial Publication link