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

This study is currently recruiting participants.
Verified January 2013 by Stanford University
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University
ClinicalTrials.gov Identifier:
NCT01108055
First received: April 15, 2010
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: Pazopanib (GW786034)
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

Resource links provided by NLM:


Further study details as provided by Stanford University:

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: 32
Study Start Date: April 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pazopanib + paclitaxel Drug: Pazopanib (GW786034)
Cycle of 28 days. Pazopanib: 800mg/day
Drug: Paclitaxel
Cycle of 28 days Paclitaxel: 80mg/m2 days 1,8 and 15

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01108055

Contacts
Contact: Denise Haas (650) 736-1252 dhaas@stanford.edu

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Denise Haas    650-736-1252    dhaas@stanford.edu   
Principal Investigator: Dr. Sandy Srinivas         
Sub-Investigator: Priti Patel         
Sub-Investigator: Lauren Harshman         
United States, Michigan
Karmanos Cancer Institute Suspended
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Sandy Srinivas
GlaxoSmithKline
Investigators
Principal Investigator: Dr. Sandy Srinivas Stanford University
  More Information

No publications provided

Responsible Party: Sandy Srinivas, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01108055     History of Changes
Other Study ID Numbers: BLDR0010, SU-04152010-5683
Study First Received: April 15, 2010
Last Updated: January 25, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014