Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC

Noah Hahn, M.D.

Status and phase

Terminated

Phase 2

Conditions

Transitional Cell Carcinoma of the Bladder

Treatments

Drug: Gemcitabine

Drug: Cisplatin

Drug: Sunitinib Malate

Procedure: Radical Cystectomy

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00859339

HOG GU07-123

Details and patient eligibility

About

This trial will investigate the activity of sunitinib combined with cisplatin and gemcitabine followed by radical cystectomy in patients with Transitional Cell Carcinoma (TCC) of the Bladder.

Full description

OUTLINE: This is a multi-center study.

Gemcitabine ( 1000 mg/m2) IV days 1 and 8
Cisplatin (70 mg/m2) IV day 1 and
Sunitinib malate (37.5 mg) oral daily for days 1-14

The treatment regimen will be administered in four, 21-day, cycles followed by radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.

ECOG performance status 0 or 1

Hematopoietic:

Absolute Neutrophil Count (ANC) > 1.5 K/mm3 [(IS): 1.5 x 109/L]
Platelets > 100 K/mm3 [(IS): 100 x 109/L]
Hemoglobin (Hgb) > 9.0 g/dL [(IS): 90 g/L]

Hepatic:

Total bilirubin < 1.5 x Upper Limit of Normal (ULN)
Aspartate aminotransferase (AST) ≤ 2.5 x ULN
Alanine aminotransferase (ALT) ≤ 2.5 x ULN

Renal:

Calculated creatinine clearance of > 60 cc/min

Cardiovascular:

No uncontrolled angina, congestive heart failure or myocardial infarction or coronary/peripheral artery bypass graft within 6 months prior to registration for protocol therapy.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III) with no evidence of metastatic disease (focal squamous and/or adenocarcinoma differentiation allowed, sarcomatoid and small-cell components not allowed). Patient with any degree of fixation of the pelvic sidewall are not eligible.
Must be willing to undergo a cystoscopy if tumor block is not available prior to registration for protocol therapy.
Eligible for radical cystectomy as per the attending urologist.
Prior radiation therapy to bone marrow is allowed to < 25% of the marrow, and must be completed at least 6 months prior to registration for protocol therapy
Written informed consent and HIPAA authorization for release of personal health information.
Age > 18 years at the time of consent.
Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

Exclusion criteria

No prior radiotherapy to the pelvis.
No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason< grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 5 years.
No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
No cerebrovascular accident or transient ischemic attack within 6 months prior to registration for protocol therapy.
No evidence of pulmonary embolism within 6 months prior to registration for protocol therapy.
No uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy).
No evidence of ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade 2.
No history of uncontrolled/untreated thyroid dysfunction.
No prolonged QTc interval (> 450 msec) on pre-entry electrocardiogram obtained within 28 days prior to being registered on study.
Patients on warfarin (>2mg) for thrombosis must be able and willing to switch to low molecular weight heparin prior to registration for protocol therapy.
No use of drugs having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide) within 7 days prior to registration for protocol therapy.
No use of CYP3A4 inhibitors (see section 5.3 for a list) within 7 days of registration for protocol therapy.
No use of CYP3A4 inducers (see section 5.3 for a list) within 14 days of registration for protocol therapy.
No use of amiodarone (CYP3A4 inhibitor) within 6 months of registration for protocol therapy.
Females must not be breastfeeding.