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

Bladder Cancer Clinical Trial

Official title:

A Phase II Study of Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01108055
• Other study ID #: BLDR0010
• Secondary ID: SU-04152010-5683
• Status: Recruiting
• Phase: Phase 2
• First received: April 15, 2010
• Last updated: July 8, 2014
• Start date: April 2010
• Est. completion date: June 2015

Study information

• Verified date: July 2014
• Source: Stanford University
• Contact: Denise Haas
• Phone: (650) 736-1252
• Email: dhaas[@]stanford.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

We will combine an oral investigational VEGF inhibitor called papopanib which is being studied in kidney cancer will be combined with standard chemotherapy called taxol in patients with relapsed recurrent urothelial cancer.

Description:

Based on the results from the Phase 1 study of pazopanib combined with paclitaxel and the activity of paclitaxel in urothelial cancer, testing this regimen in a disease where there is an unmet need appears appropriate.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: June 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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

Drug:
• Pazopanib (GW786034)
Cycle of 28 days. Pazopanib: 800mg/day
• Paclitaxel
Cycle of 28 days Paclitaxel: 80mg/m2 days 1,8 and 15

Locations

Country	Name	City	State
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall objective tumor response rate (CR, PR) per RECIST criteria.		Every 8 weeks	No
Secondary	Progression Free Survival		every 8 weeks	No
Secondary	Safety as assessed by CTC		every 4 weeks	Yes
Secondary	Measure: Safety as assessed by common toxicity criteria		4 weeks	Yes