Phase II Trial of Abraxane in Front Line Therapy of Hormone Refractory Metastatic Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Kaiser Permanente
ClinicalTrials.gov Identifier:
NCT00284752
First received: January 30, 2006
Last updated: September 28, 2012
Last verified: September 2012
  Purpose

Evaluate the efficacy of Abraxane in first line chemotherapy of patients with hormone refractory metastatic prostate cancer, based on prostate specific antigen (PSA) response


Condition Intervention Phase
Prostate Cancer
Drug: Abraxane
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Abraxane in Front Line Therapy of Hormone Refractory Metastatic Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Kaiser Permanente:

Primary Outcome Measures:
  • Evaluate the efficacy of Abraxane in first line chemotherapy of patients with [ Time Frame: August 2008 ] [ Designated as safety issue: Yes ]
  • hormone refractory metastatic prostate cancer, based on prostate specific antigen (PSA) response [ Time Frame: August 2008 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the effect of Abraxane on,Time to PSA progression, Measurable tumor response rate (if measureable disease at baseline), Overall survival [ Time Frame: August 2008 ] [ Designated as safety issue: No ]
  • Evaluate the toxicity of Abraxane in this group of patients. [ Time Frame: August 2008 ] [ Designated as safety issue: Yes ]

Enrollment: 56
Study Start Date: August 2005
Study Completion Date: December 2011
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABI-007 Drug: Abraxane
This is a Phase II single-arm study for first-line chemotherapy of patients with hormone refractory metastatic prostate cancer. Eligible patients will be chemotherapy naive and will receive weekly Abraxane 100mg/m2 IV over 30 minutes. These will be 4-week cycles with patients receiving Abraxane 100 mg/m2 weekly for 3 weeks and one week off for rest. Patients will continue on therapy until disease or PSA

Detailed Description:

Taxanes are the most widely tested and effective chemotherapy drugs for hormone refractory prostate cancer. Weekly paclitaxel was reported to produce 25-39% PSA responses in first line and up to 33% in second line chemotherapy of patients with prostate cancer in early clinical trials (1, 2). Paclitaxel activity in prostate cancer is schedule dependent, and weekly paclitaxel was reported to produce highest response rates (1, 2). Docetaxel was recently approved by the Food and Drug Administration for treatment of hormone refractory metastatic prostate cancer, since it is the only chemotherapy drug with documented improvement in survival in this group of patients. Docetaxel was associated with 45.8% overall grade 3/4 toxicities and it has to be given with steroid pre-medication. This regimen might be difficult to use in advanced prostate cancer patients that are often elderly and with multiple co-morbid conditions.

ABI-007 [Abraxane™ (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)] is the first in its class of biologically interactive albumin-bound forms of chemotherapy (3). This composition provides a novel approach of increasing intra-tumoral concentration of the drug by a receptor-mediated transport process allowing transcytosis across the endothelial cell wall, thereby breaching the blood/tumor interface. This albumin-specific receptor mediated process involves the binding of a specific receptor (gp60) on the endothelial cell wall, resulting in activation of a protein caveolin-1, which initiates an opening in the endothelial wall with formation of a little caves or caveolae, with transport of the albumin-bound chemotherapeutic complex via these caveolae to the underlying tumor interstitium (4). A protein specifically secreted by the tumor (SPARC) binds and entraps the albumin, allowing release of the hydrophobic drug to the tumor cell membrane. ABI-007 is the first biologically interactive albumin-bound chemotherapy agent leveraging this gp-60/caveolin-1/caveolae/Sparc pathway to increase intra-tumoral concentration of the drug and reduce the amount of the toxic chemotherapy in normal tissue.

Preclinical studies comparing Abraxane to paclitaxel demonstrated lower toxicities, with a maximum tolerated dose (MTD) approximately 50% higher for Abraxane (7) compared to paclitaxel (11). At equal doses there was less myelosuppression and improved efficacy than paclitaxel in a xenograft tumor model of human mammary adenocarcinoma. Clinical studies confirmed improved toxicity profile and higher response rates, in metastatic breast cancer, of Abraxane compared to cremophor EL paclitaxel (Taxol) (5, 8). The weekly regimen was shown to be active even in patients with cancers refractory to paclitaxel, docetaxel or when Abraxane was given after both agents (8).

  Eligibility

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

Inclusion Criteria:

  1. Histopathologically or cytologically proven adenocarcinoma of the prostate metastatic to the bones or lymph nodes as documented by bone scan or CT scan with evidence of progression despite standard hormonal management (orchiectomy, GNRH agonist, or GNRH antagonist-hormone refractory). No major organ allowed
  2. No prior chemotherapy
  3. For patients who have been on anti-androgen therapy, patients must have progressive disease after anti-androgen withdrawal (6 weeks biclutamide or nilutamide, 4 weeks for flutamide).
  4. PSA progression is defined as rising PSA.

Exclusion Criteria:

  1. Active malignancy other than non-melanoma skin cancer within 5 years of enrollment.
  2. Significant active medical illness which in the opinion of the investigator will preclude treatment.
  3. Brain metastasis, any non-bone metastasis except lymph node metastasis
  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: NCT00284752

Locations
United States, California
Kaiser Permanente
Vallejo, California, United States, 94589
Sponsors and Collaborators
Kaiser Permanente
Celgene Corporation
Investigators
Principal Investigator: Tatjana Kolevska, MD Kaiser Permanente
  More Information

No publications provided

Responsible Party: Kaiser Permanente
ClinicalTrials.gov Identifier: NCT00284752     History of Changes
Other Study ID Numbers: TK001
Study First Received: January 30, 2006
Last Updated: September 28, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Kaiser Permanente:
Prostate
Cancer
Metastatic

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hormones
Paclitaxel
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014