Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01108055
• Date of registration: 15/04/2010
• Primary sponsor: Sandy Srinivas
• Public title: Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer
• Scientific title: A Phase II Study of Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer
• Date of first enrolment: April 2010
• Target sample size: 32
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01108055
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Denise Haas

• Name: Dr. Sandy Srinivas
• Affiliation: Stanford University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Histologically confirmed transitional cell carcinoma (TCC) of the urothelium
(bladder, renal pelvis, ureter, or urethra). Mixed histology is allowed as long as
the predominant histology is TCC

2. First recurrence after treatment with a maximum of two chemotherapeutic regimens.

3. Subjects must provide written informed consent prior to performance of study-specific
procedures or assessments, and must be willing to comply with treatment and follow
up.

Procedures conducted as part of the subject's routine clinical management (e.g.,
blood count, imaging study) and obtained prior to signing of informed consent may be
utilized for screening or baseline purposes provided these procedures are conducted
as specified in the protocol.

4. Age >= 18 years

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

6. Measurable disease criteria by RECIST criteria

7. Adequate organ system function as defined below

1. Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

2. Hemoglobin >= 9 g/dL

3. Platelets >= 100 X 10^9/L

4. Prothrombin time (PT) or international normalized ratio (INR) <= 1.2 X upper
limit of normal (ULN)

5. Total bilirubin <= 1.5 X ULN

6. AST and ALT <= 2.5 X ULN

7. Serum creatinine <= 1.8 mg/dL

8. Urine Protein to Creatinine Ratio (UPC) <1

8. A female is eligible to enter and participate in this study if she is of
non-childbearing potential (i.e., physiologically incapable of becoming pregnant).
This includes any female who has had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Menopause

Childbearing potential females must have a negative serum pregnancy test within 2 weeks
prior to the first dose of study treatment, preferably as close to the first dose as
possible, and agree to use adequate contraception. Adequate acceptable contraceptive
methods, when used consistently and in accordance with both the product label and the
instructions of the physician, are as follow:

- An intrauterine device with a documented failure rate of less than 1% per year.

- Vasectomized partner who is sterile prior to the female subject's entry and is the
sole sexual partner for that female.

- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days after
the last dose of investigational product.

- Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

Exclusion Criteria:

1. History of other malignancies within 5 years prior to Day 1 except for tumors with a
negligible risk for metastasis or death, such as adequately controlled basal cell
carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix,
early-stage bladder cancer, or low-grade endometrial cancer Malignancies that have
undergone a putative surgical cure (i.e., localized prostate cancer
post-prostatectomy) within 5 years prior to Day 1 may be discussed with the Medical
Monitor

2. History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for 6 months prior to first dose of study drug.

3. Clinically significant gastrointestinal abnormalities that may increase the risk for
GI bleeding

4. Clinically significant gastrointestinal abnormalities that may affect absorption of
the investigational product

5. Presence of uncontrolled infection.

6. Prolongation of corrected QT interval (QTc) > 480 milliseconds. On antiarrhythmics or
medications known to prolong QT interval

7. History of any one or more of the following cardiovascular conditions within the past
6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Coronary artery by-pass graft surgery

- Symptomatic peripheral vascular disease

- Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA)

8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140
mmHg or diastolic blood pressure (DBP) of >= 90mmHg].

9. History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically
significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT)
within the past 6 months

10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture

11. Evidence of active bleeding or bleeding diathesis.

12. Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to procedures.

13. Patients on strong CYP3A4 inhibitors

14. Uncorrected abnormal electrolytes- K, Mg and Ca

15. Prior treatment with taxane chemotherapy

16. Treatment with any of the following anti-cancer therapies:

- radiation therapy, surgery or tumor embolization within 14 days prior to the
first dose of pazopanib OR

- chemotherapy, immunotherapy, biologic therapy, investigational therapy or
hormonal therapy within 14 days or five half-lives of a drug (whichever is
longer) prior to the first dose of pazopanib



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Bladder (Urothelial, Transitional Cell) Cancer

Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable

Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy)

Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive)

Bladder Cancer

Intervention(s)

Drug: Paclitaxel

Drug: Pazopanib (GW786034)

Primary Outcome(s)

Overall objective tumor response rate (CR, PR) per RECIST criteria. [Time Frame: Every 8 weeks]

Secondary Outcome(s)

Measure: Safety as assessed by common toxicity criteria [Time Frame: 4 weeks]

Progression Free Survival [Time Frame: every 8 weeks]

Safety as assessed by CTC [Time Frame: every 4 weeks]

Secondary ID(s)

BLDR0010

SU-04152010-5683

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline