Clinical trial NCT00583349: Intravesicular Abraxane for Treatment-Refractory Bladder Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bladder Cancer
Keywords: Bladder Cancer
Chemotherapy
Bladder Neoplasms
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2007-12-31
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
timeFrame: 6 weeks
measure: Number of Participants With Complete Response (CR) or No Response (NR) After Treatment
timeFrame: 6 weeks
Secondary outcomes:
measure: To Further Evaluate the Safety and Toxicity Profile of Intravesically Administered Abraxane Therapy.
timeFrame: 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Herbert Irving Pavillion 11th Floor
state: New York
Study officials:
affiliation: Columbia University Irving Medical Center, Urology
name: James M McKiernan, MD
role: PRINCIPAL_INVESTIGATOR
References: