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)

Cardiff University

Status and phase

Completed

Phase 2

Conditions

Transitional Cell Cancer of the Renal Pelvis and Ureter

Bladder Cancer

Urethral Cancer

Treatments

Drug: gemcitabine hydrochloride

Drug: sunitinib malate

Drug: cisplatin

Study type

Interventional

Funder types

Other

Identifiers

NCT01089088

EUDRACT-2007-007591-42

EU-21013

CDR0000667764

WCTU-SPON-416-07

CRUK-07/044

ISRCTN54607216

WCTU-SUCCINCT

Details and patient eligibility

About

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.

Full 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

Enrollment

63 patients

Sex

All

Ages

16 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)