Intravesicular Abraxane for Treatment-Refractory Bladder Cancer (Abraxane)

A Combined Phase I and Phase II Trial of Intravesical Abraxane, a Biologically Interactive Albumin-bound Paclitaxel, in the Treatment of Refractory Non-muscle Invasive and in T2 Transitional Cell Bladder Cancer

Phase I:

To determine the safety, toxicity and efficacy profiles of intravesically administered Abraxane at the Maximum Tolerated Dose.

To assemble tissue bank to assess molecular correlates for response to intravesical Abraxane therapy. The antibodies analyzed will include p53, p63, Stathmin, Tau and Ki67.

Phase II:

To evaluate the utility (potential for clinical efficacy) of Abraxane in the treatment of refractory non-muscle invasive and a subset of T2 TCC of the bladder as measured by response rate (defined as negative cytology and bladder biopsy).

To further evaluate the safety and toxicity profile of intravesically administered Abraxane therapy.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Abraxane

Detailed Description

In 2006, it is estimated that 61,420 cases of bladder cancer will be diagnosed in the United States and 13,060 people will die from the disease. This makes bladder cancer the fourth leading cause of cancer in men and the ninth leading cause of cancer in women in the United States. Non-muscle invasive bladder cancer accounts for 70 to 80 percent of these cases and the natural history can vary widely with recurrence being common. In individual cases with high-risk clinical and pathological features (Ta, Tis, and T1) the use of intravesical therapy following complete transurethral resection of the tumor has become the standard of care. However up to 50 percent of patients treated with intravesical therapy for high-risk non-muscle invasive bladder cancer will recur. Response rates to second-line intravesical therapy are 20 percent or less in this population. Innovations in the efficacy of intravesical agents also have applications within a subset of patients with muscle-invasive disease who are undergoing complete transurethral resection in conjunction with local chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Herbert Irving Pavillion 11th Floor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have a diagnosis of transitional cell carcinoma (TCC) of the urinary bladder confirmed at the study institution. The patient must have demonstrated superficial recurrent bladder cancer refractory to standard intravesical therapy. This will include stage Ta, T1, Tis and exclude all patients with muscle invasion (T2). All patients with stage Ta will require documentation of high-grade histology. All grossly visible disease must be fully resected and pathologic stage will be confirmed at the institution where the patient is enrolled. Patients must exhibit disease recurrence after receiving some form of standard intravesical therapy, including Bacillus Calmette-Guerin (BCG), mitomycin, interferon or any combination thereof.
• Age > 18 and must be able to read, understand and sign informed consent
• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0,1 (See Appendix II )
• Peripheral neuropathy: must be < grade 1

• Hematologic-Inclusion within 2 weeks of start of treatment

  • Absolute neutrophil count > 1,500/mm3
  • Hemoglobin >9.0 g/dl
  • Platelet count > 100,000/mm3

• Hepatic-Inclusion within 2 weeks of entry

  • Total Bilirubin must be within normal limits.
  • Adequate renal function with serum creatinine ≤ 2.0 mg/dL
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) for the institution, Alkaline phosphatase ≤ 2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis
• Women of childbearing potential must have a negative pregnancy test.
• All patients of childbearing potential must be willing to consent to using effective contraception, i.e., intrauterine device (IUD), Birth control pills, Depo-Provera, and condoms while on treatment and for 3 months after their participation in the study ends.
• No intravesical therapy within 6 weeks of study entry
• No prior radiation to the pelvis

Exclusion Criteria:

• Prior systemic docetaxel or paclitaxel therapy.
• Any other malignancy diagnosed within 2 years of study entry (except basal or squamous cell skin cancers or non-invasive cancer of the cervix) is excluded.
• Concurrent treatment with any chemotherapeutic agent.
• Women who are pregnant or lactating.
• History of vesicoureteral reflux or an indwelling urinary stent.
• Participation in any other research protocol involving administration of an investigational agent within 3 months prior to study entry aside from the phase I segment of this study.
• History of neuropathy of any cause

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Abraxane administration; Phase I and Phase II: Patients will receive intravesical Abraxane by sterile urethral catheterization once weekly for six weeks. Phase II: If a complete response after six weekly installations is achieved, patients will receive additional monthly maintenance instillations until there is a positive cystoscopic biopsy or until a maximum of six additional instillations have been administered.

Drug: Abraxane; Abraxane is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Intravesically administered, dose escalation, 6 weekly instillations; Other Names: Paclitaxel protein-bound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)	To determine the safety, toxicity and efficacy profiles of intravesically administered Abraxane at the Maximum Tolerated Dose (MTD). A DLT is defined by the National Cancer Institute Common Toxicity Criteria version 3.0	6 weeks
Number of Participants With Complete Response (CR) or No Response (NR) After Treatment	To evaluate the utility (potential for clinical efficacy) of Abraxane in the treatment of refractory superficial transitional cell carcinomas (TCC) as measured by response rate (defined as negative cytology and bladder biopsy). Patients were considered to have a complete response if they had a negative biopsy and negative cytology. All patients with positive biopsies or cytology were classified as having no response.	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To Further Evaluate the Safety and Toxicity Profile of Intravesically Administered Abraxane Therapy.	6 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: James M McKiernan, MD, Columbia University Irving Medical Center, Urology

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 20, 2007
• First Posted (Estimated): December 31, 2007

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Chemotherapy; Bladder Cancer; Bladder Neoplasms
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Paclitaxel
• Other Study ID Numbers: AAAC1114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED