Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer
This study is currently recruiting participants.
Verified January 2013 by Stanford University
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University
First received: April 15, 2010
Last updated: January 25, 2013
Last verified: January 2013
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.
Bladder (Urothelial, Transitional Cell) Cancer
Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive)
Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy)
Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable
Drug: Pazopanib (GW786034)
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Study of Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer
Primary Outcome Measures:
- Overall objective tumor response rate (CR, PR) per RECIST criteria. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Progression Free Survival [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
- Safety as assessed by CTC [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
- Measure: Safety as assessed by common toxicity criteria [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2013 (Final data collection date for primary outcome measure)
Experimental: pazopanib + paclitaxel
Drug: Pazopanib (GW786034)
Cycle of 28 days. Pazopanib: 800mg/day
Cycle of 28 days Paclitaxel: 80mg/m2 days 1,8 and 15
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
- First recurrence after treatment with a maximum of two chemotherapeutic regimens.
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.
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Measurable disease criteria by RECIST criteria
Adequate organ system function as defined below
- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L
- Hemoglobin >= 9 g/dL
- Platelets >= 100 X 10^9/L
- Prothrombin time (PT) or international normalized ratio (INR) <= 1.2 X upper limit of normal (ULN)
- Total bilirubin <= 1.5 X ULN
- AST and ALT <= 2.5 X ULN
- Serum creatinine <= 1.8 mg/dL
- Urine Protein to Creatinine Ratio (UPC) <1
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
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).
- 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
- 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.
- Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding
- Clinically significant gastrointestinal abnormalities that may affect absorption of the investigational product
- Presence of uncontrolled infection.
- Prolongation of corrected QT interval (QTc) > 480 milliseconds. On antiarrhythmics or medications known to prolong QT interval
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)
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg].
- History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture
- Evidence of active bleeding or bleeding diathesis.
- 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.
- Patients on strong CYP3A4 inhibitors
- Uncorrected abnormal electrolytes- K, Mg and Ca
- Prior treatment with taxane chemotherapy
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01108055
|Stanford University School of Medicine
|Stanford, California, United States, 94305 |
|Contact: Denise Haas 650-736-1252 firstname.lastname@example.org |
|Principal Investigator: Dr. Sandy Srinivas |
|Sub-Investigator: Priti Patel |
|Sub-Investigator: Lauren Harshman |
|Karmanos Cancer Institute
|Detroit, Michigan, United States, 48201 |
||Dr. Sandy Srinivas
No publications provided
||Sandy Srinivas, Associate Professor of Medicine, Stanford University
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 15, 2010
||January 25, 2013
||United States: Food and Drug Administration
United States: Institutional Review Board
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Urinary Bladder Neoplasms
Neoplasms, Second Primary
Neoplasms by Site
Urinary Bladder Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic