Phase I Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma

This study is currently recruiting participants.
Verified March 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborator:
Endo Pharmaceuticals
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01606345
First received: May 23, 2012
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Urothelial Carcinoma
Drug: Valrubicin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation and Landmark Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma (UTUC) Following Endoscopic Resection

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Number of Participants with Recurrence Free Survival (RFS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 21
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I Dose Escalation
Dose escalation: 200 mg/75 ml effluent, 400 mg/75 ml effluent, 800 mg/75 ml effluent
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • Uncontrolled urinary tract infection based on a combination of urinalysis and urine culture
  • 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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01606345

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Inez Sims    813-745-3892    inez.sims@moffitt.org   
Principal Investigator: Wade Sexton, M.D.         
Sub-Investigator: Mayer Fishman, M.D., Ph.D.         
Sub-Investigator: Julio Pow-Sang, M.D.         
Principal Investigator: Shohreh Dickinson, M.D.         
Sub-Investigator: Philippe Spiess, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Endo Pharmaceuticals
Investigators
Principal Investigator: Wade Sexton, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01606345     History of Changes
Other Study ID Numbers: MCC-16722
Study First Received: May 23, 2012
Last Updated: March 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Upper Tract Urothelial Carcinoma
UTUC
Kidney
Cancer
Renal

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Valrubicin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014