Phase I Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma

NCT01606345 | Completed Phase 1 DMC

• 1 other identifier: MCC-16722
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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).

Conditions

Urothelial Carcinoma

Keywords

Upper Tract Urothelial Carcinoma; UTUC; Kidney; Cancer; Renal

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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 Outcomes (2)

• Number of Participants with Recurrence Free Survival (RFS)

  12 months

• Number of Participants with Progression Free Survival (PFS)

  12 months

Study Arms (1)

Phase I Dose Escalation

EXPERIMENTAL

Dose escalation: 200 mg/75 ml effluent, 400 mg/75 ml effluent, 800 mg/75 ml effluent

Drug: Valrubicin

Interventions

Valrubicin DRUG

Eligible patients will receive percutaneous valrubicin beginning no sooner than 10 days following nephrostomy placement and within 6 weeks of tumor treatment/resection.

Also known as: ValstarTM

Phase I Dose Escalation

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Endo Pharmaceuticals: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasms

Interventions

valrubicin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Wade Sexton, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2012
• First Posted: May 25, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 22, 2016

Record last verified: 2016-04

Locations

US (1)