Phase I Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma

April 21, 2016 updated by: H. Lee Moffitt Cancer Center and Research Institute

Phase I Dose Escalation and Landmark Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma (UTUC) Following Endoscopic Resection

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • ValstarTM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Endo Pharmaceuticals

Investigators

  • Principal Investigator: Wade Sexton, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

May 23, 2012

First Submitted That Met QC Criteria

May 24, 2012

First Posted (Estimate)

May 25, 2012

Study Record Updates

Last Update Posted (Estimate)

April 22, 2016

Last Update Submitted That Met QC Criteria

April 21, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-16722

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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