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Phase I Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01606345
Recruitment Status : Completed
First Posted : May 25, 2012
Last Update Posted : April 22, 2016
Sponsor:
Collaborator:
Endo Pharmaceuticals
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE May 23, 2012
First Posted Date  ICMJE May 25, 2012
Last Update Posted Date April 22, 2016
Study Start Date  ICMJE July 2012
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2012)
Maximum Tolerated Dose (MTD) [ Time Frame: 12 months ]
To define the maximum-tolerated dose (MTD) in a multiple dose regimen of valrubicin administered through a percutaneous nephrostomy tube placed following endoscopic resection (percutaneous or ureteroscopic) of UTUC
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2012)
  • Number of Participants with Recurrence Free Survival (RFS) [ Time Frame: 12 months ]
    To evaluate the landmark (1 year) recurrence free survival (RFS). Recurrence is defined as any tumor recurrence in the upper tract following initiation of percutaneous valrubicin.
  • Number of Participants with Progression Free Survival (PFS) [ Time Frame: 12 months ]
    To evaluate the landmark (1 year) progression free survival (PFS) post valrubicin treatment. Progression is defined as a tumor recurrence in the upper tract of higher clinical stage and/or higher tumor grade following initiation of percutaneous valrubicin.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma
Official Title  ICMJE Phase I Dose Escalation and Landmark Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma (UTUC) Following Endoscopic Resection
Brief Summary The purpose of this study is to learn more about how well the drug valrubicin (VALSTAR®) works to help treat the patient's cancer when administered through a nephrostomy tube inserted through their back into their kidney. The study is also being done to determine how safe and easy it is to tolerate valrubicin at specific dose levels, as well as the way in which the drug is eliminated from the human body (Pharmacokinetics or PK).
Detailed Description Eligible patients will receive percutaneous valrubicin beginning no sooner than 10 days following nephrostomy placement and within 6 weeks of tumor treatment/resection. Therapy will be administered at one of three dose levels in a 3 + 3 design (200 mg/75 ml diluent, 400 mg/75 ml diluent or 800 mg/75 ml diluent). It is anticipated that at least 3 patients will be accrued at both of the 200 and 400 mg dose levels. Assuming acceptable toxicity, the accrual target for the 800 mg dose level will be 9 patients. If the maximum tolerated dose is determined to be 200 mg or 400 mg, expansion to 9 patients will occur at the maximum tolerated dose (MTD) dose level. Drug will be administered on a weekly basis for 8 total treatments.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma
Intervention  ICMJE Drug: Valrubicin
Eligible patients will receive percutaneous valrubicin beginning no sooner than 10 days following nephrostomy placement and within 6 weeks of tumor treatment/resection.
Other Name: ValstarTM
Study Arms  ICMJE Experimental: Phase I Dose Escalation
Dose escalation: 200 mg/75 ml effluent, 400 mg/75 ml effluent, 800 mg/75 ml effluent
Intervention: Drug: Valrubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 16, 2015)
4
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2012)
21
Actual Study Completion Date  ICMJE April 2016
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Zubrod: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Tissue confirmation of UTUC
  • Available tumor grade information
  • Treated UTUC (complete resection and or fulguration of tumor as is safely possible, based on the judgment of the investigators and based on visual inspection of the involved kidney and ureter) and at least one of the following:

    • Low grade urothelial carcinoma
    • Percutaneous upper tract Bacillus Calmette-Guérin (BCG) failure and: High grade urothelial carcinoma or Carcinoma in situ (CIS) with imperative indications for nephron preservation (solitary kidney, renal insufficiency, bilateral upper tract tumors, etc.) as determined by study Principal Investigators (PIs)
    • Contraindications to percutaneous BCG (e.g. previous adverse systemic or local reaction to BCG exposure as judged by PIs, or immunosuppression, or other contraindications to BCG therapy) and: High grade urothelial carcinoma or CIS with imperative indications for nephron preservation (solitary kidney, renal insufficiency, bilateral upper tract tumors, etc.) as determined by study PIs
  • Normal prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR)
  • Platelets 100 x 10^9/l or greater
  • Absolute neutrophil count (ANC) 1.5 x 10^9/l or greater
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 3 x upper limits of normal (ULN) or less
  • Able to receive valrubicin within 6 weeks of the initial surgery or within 6 weeks of a second look surgical procedure

Exclusion Criteria:

  • Radiographic or pathologic evidence for locally advanced (muscle invasion, lymphovascular invasion, lymphadenopathy, renal parenchymal invasion) or distant metastatic disease
  • Contraindications for percutaneous nephrostomy (i.e. bleeding diathesis and/or patients who must be maintained on therapeutic doses of warfarin or antiplatelet agents while valrubicin is being administered). Note: 81 mg aspirin acceptable.
  • Evidence for renal/ureteral obstruction as determined by radiographic studies (antegrade nephrostogram, Intravenous pyelography (IVP), Computed tomography (CT) urogram, retrograde pyelogram, lasix renogram, or a combination thereof)
  • Contraindication to percutaneous administration of valrubicin, a metabolite of valrubicin, or known hypersensitivity to anthra-cyclines or polyoxyl castor oil.
  • Symptomatic urinary tract infection based on a combination of urinalysis and urine culture and patient symptoms (i.e. Fever). Investigators expect patients to have an abnormal urinalysis based on indwelling urinary devices and prior surgical treatment.
  • Urolithiasis in the involved ipsilateral kidney (not including punctuate calcifications or suspected renal parenchymal or papillary tip calcifications seen on radiographic studies or visualized endoscopically)
  • Patient on renal replacement therapy (hemodialysis or peritoneal dialysis)
  • Extravasation of contrast as visualized on antegrade nephrostogram studies. (Note: At the initial nephrostogram possibly performed in the operating room or with initial percutaneous nephrostomy placement, extravasation can be visualized. However, a procedure prior to drug administration confirms there is not further extravasation present).
  • Concurrent malignancy (except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or concurrent non-muscle invasive bladder cancer that has been completely resected)
  • Congenital or acquired immunodeficiency
  • Positive pregnancy test or plans for future pregnancy
  • Expected poor compliance as judged by the investigators
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01606345
Other Study ID Numbers  ICMJE MCC-16722
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Endo Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Wade Sexton, M.D. H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP