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

NCT00585689 | Completed Phase 2 Results DMC

• 2 other identifiers: UMCC 2007.061HUM 13486
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Locally advanced urothelial carcinoma of the bladder

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment

  The rate of pathologic complete response (pT0) following three 21 day cycles of neoadjuvant ABI-007, carboplatin and gemcitabine was determined.

  63 days (post 3 cycles)

Study Arms (1)

Neoadjuvant ABI-007, Carboplatin, and Gemcitabine

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Gemcitabine; Procedure: Radical Cystectomy

Interventions

ABI-007 DRUG

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.

Neoadjuvant ABI-007, Carboplatin, and Gemcitabine

Carboplatin DRUG

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.

Neoadjuvant ABI-007, Carboplatin, and Gemcitabine

Gemcitabine DRUG

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.

Neoadjuvant ABI-007, Carboplatin, and Gemcitabine

Radical Cystectomy PROCEDURE

Neoadjuvant ABI-007, Carboplatin, and Gemcitabine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Grivas PD, Hussain M, Hafez K, Daignault-Newton S, Wood D, Lee CT, Weizer A, Montie JE, Hollenbeck B, Montgomery JS, Alva A, Smith DC. A phase II trial of neoadjuvant nab-paclitaxel, carboplatin, and gemcitabine (ACaG) in patients with locally advanced carcinoma of the bladder. Urology. 2013 Jul;82(1):111-7. doi: 10.1016/j.urology.2013.03.044. Epub 2013 May 21.

  PMID: 23706253 RESULT

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Albumin-Bound Paclitaxel; Carboplatin; Gemcitabine; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. David Smith, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

dcsmith@umich.edu

734-936-6884

Study Officials

• David C Smith, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 3, 2008
• Study Start: December 1, 2007
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: November 30, 2015
• Results First Posted: June 5, 2014

Record last verified: 2015-11

Locations

US (1)