Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Locally Advanced Bladder Cancer

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
David C Smith, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00585689
First received: December 26, 2007
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

Study participants will have been diagnosed with bladder cancer that has invaded the muscle wall of the bladder. Surgery is used to remove cancer when it is in the muscle of the bladder. Unfortunately, approximately 50% of people may have their cancer return in another location. For this reason, researchers are focusing on new chemotherapy regimens to be given before surgery (to remove the bladder) that may decrease the likelihood of cancer spreading.

Paclitaxel, carboplatin and gemcitabine are chemotherapy drugs known to destroy bladder cancer cells.

ABI-007 (brand name Abraxane™) is a form of the chemotherapy drug called paclitaxel. Standard paclitaxel is formulated with ethanol and a substance called Cremophor EL (polyoxyethylated castor oil). However, these additives are felt to contribute to the side effects (possibly severe) associated with paclitaxel. ABI-007 does not contain these additives and may deliver more drug to tumor cells. ABI-007 is approved by the United States Food and Drug Administration (FDA) in the treatment of metastatic (advanced) breast cancer, and is being evaluated in other cancers in research studies.

This study will evaluate the safety and efficacy of the combination of ABI-007, carboplatin and gemcitabine in the treatment of bladder cancer prior to surgery to remove the bladder.


Condition Intervention Phase
Bladder Cancer
Drug: ABI-007
Drug: Carboplatin
Drug: Gemcitabine
Procedure: Radical Cystectomy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Two Trial of Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Patients With Locally Advanced Carcinoma of the Bladder

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment [ Time Frame: 63 days (post 3 cycles) ] [ Designated as safety issue: No ]
    The rate of pathologic complete response (pT0) following three 21 day cycles of neoadjuvant ABI-007, carboplatin and gemcitabine was determined.


Secondary Outcome Measures:
  • Assess the Ability to Predict Response to Chemotherapy Using Gene Expression Profiles and SPARC in Tumor Specimens [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: December 2007
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neoadjuvant ABI-007, Carboplatin, and Gemcitabine
Neoadjuvant ABI-007 (260 mg/m^2) on day 1, Carboplatin (Target AUC [Area under the curve] =5) on day 1, and Gemcitabine (800 mg^m2) on days 1 and 8, every 21 days.
Drug: ABI-007
ABI-007 will be administered at a dose of 260 mg/m2 over a 30 min IV infusion on day 1 of each 21 day cycle.
Drug: Carboplatin
Carboplatin will be administered at a dose of TARGET AUC=5 over a 15 min IV infusion of day 1 of each 21 day cycle.
Drug: Gemcitabine
Gemcitabine will be administered at a dose of 800 mg/m2 over a 30 min IV infusion on days 1 and 8 of each 21 day cycle.
Procedure: Radical Cystectomy

  Eligibility

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

Inclusion Criteria:

  • Histologically proven locally advanced (T2-4,N0,M0 or Tany,N1-3,M0) urothelial carcinoma of the bladder and be candidates for cystectomy following chemotherapy. Tumor specimens must be available for assay of molecular markers (correlative research).
  • Performance status of 0, 1 or 2 by Eastern Cooperative Oncology Group (ECOG) criteria.
  • Serum creatinine <2.0 mg/dl and/or creatinine clearance >40 ml/min.
  • Granulocyte count > 1,500/mm3, platelet > 100,000/mm3, and hemoglobin > 9.0 g/dl.
  • Adequate liver functions: AST and ALT < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, and bilirubin < 1.5 mg/dl.
  • Pre-existing peripheral neuropathy > grade 2
  • Recovered from any effects of surgery.
  • Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Women with reproductive potential must have a negative pregnancy test.

Exclusion Criteria:

  • Prior systemic or intra-arterial chemotherapy and rior radiotherapy. (intravesical chemotherapy allowed.)
  • Pre-existing peripheral neuropathy > grade 2
  • Prior malignancy [except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for 2 years]
  • Unresolved bacterial infection requiring active treatment with antibiotics. (Treatment may begin at the conclusion of antibiotic therapy.)
  • Pregnant or lactating women may not participate.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00585689

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Celgene Corporation
Investigators
Principal Investigator: David C Smith, MD University of Michigan
  More Information

Publications:
Responsible Party: David C Smith, Professor of Internal Medicine, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00585689     History of Changes
Other Study ID Numbers: UMCC 2007.061, HUM 13486
Study First Received: December 26, 2007
Results First Received: May 5, 2014
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
Locally advanced urothelial carcinoma of the bladder

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Carboplatin
Gemcitabine
Paclitaxel
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014