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

NCT01108055 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB-17472SU-04152010-5683BLDR0010
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 2

Brief Summary

We will combine an oral investigational vascular endothelial growth factor (VEGF inhibitor) called pazopanib which is being studied in kidney cancer will be combined with standard chemotherapy called taxol in patients with relapsed recurrent urothelial cancer.

Conditions

Bladder Cancer; 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

Outcome Measures

Primary Outcomes (1)

• Objective Tumor Response

  The tumor response rate was assessed per the Response Evaluation Criteria In Solid Tumors (RECIST). RECIST criteria are a set of published rules that define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. RECIST criteria offer a simplified and conservative extraction of imaging data suitable for wide application in clinical trials. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories: * Complete response (CR) = Disappearance of all target lesions * Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions * Stable disease (SD) = Small changes that do not meet above criteria Objective tumor response means those with response better than stable disease, ie, complete response (CR) + partial response (PR).

  Every 8 weeks

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  4 years

• Overall Response Rate

  4 years

• Overall Survival

  4 years

• Median Overall Survival (OS) by Bellmunt Score

  4 years

Study Arms (1)

pazopanib + paclitaxel

EXPERIMENTAL

Cycle of 28 days. Pazopanib: 800mg daily Cycle of 28 days Paclitaxel: 80mg/m2 on days 1,8 and 15

Drug: Pazopanib (GW786034); Drug: Paclitaxel

Interventions

Pazopanib (GW786034) DRUG

Cycle of 28 days. Pazopanib: 800mg/day

Also known as: GW786034

pazopanib + paclitaxel

Paclitaxel DRUG

Cycle of 28 days Paclitaxel: 80mg/m2 days 1,8 and 15

Also known as: Taxol

pazopanib + paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (eg, 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 to 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
• aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT)≤ 2.5 x ULN
• Serum creatinine ≤ 1.8 mg/dL

You may not qualify if:

• 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 (ie, 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 \[defined as systolic blood pressure (SBP) of ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90mm Hg\].
• History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months

Sponsors & Collaborators

• Sandy Srinivas: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

pazopanib; Paclitaxel

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Sandy Srinivas, MD
• Organization: Stanford University

sandysri@stanford.edu

650 498 6000

Study Officials

• Dr. Sandy Srinivas

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 15, 2010
• First Posted: April 21, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: July 1, 2015
• Last Updated: June 9, 2017
• Results First Posted: June 9, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)