Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced or Refractory Solid Tumors

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00499291
First received: July 10, 2007
Last updated: September 25, 2008
Last verified: October 2007
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This clinical trial is studying how well paclitaxel albumin-stabilized nanoparticle formulation works in treating patients with advanced or refractory solid tumors.


Condition Intervention
Cancer
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Procedure: gene expression analysis
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Procedure: polymerase chain reaction

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study of Nab-Paclitaxel (Nanoparticle Albumin Bound-Paclitaxel) in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Inter-individual pharmacokinetic variability [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters [ Designated as safety issue: No ]
  • Neutropenia [ Designated as safety issue: No ]
  • CYP2C8*3 variant expression [ Designated as safety issue: No ]
  • Genetic variance relating to pharmacokinetics and toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 129
Study Start Date: September 2006
Estimated Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To develop a population pharmacokinetic model for paclitaxel administered as paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) to a large population of patients with advanced or refractory cancer to characterize the inter-individual pharmacokinetic variability of this agent.

Secondary

  • To explore nab-paclitaxel pharmacokinetic parameters in patients with metastatic prostate cancer (castrate), metastatic breast cancer, advanced non-small cell lung cancer and other incurable advanced or refractory tumors amenable to treatment with nab-paclitaxel.
  • To explore the association between exposure to total and unbound paclitaxel after administration of nab-paclitaxel and neutropenia.
  • To explore the association between the CYP2C8*3 variant and paclitaxel clearance.
  • To explore the association between other variants of CYP2C8 and other genes involved in paclitaxel disposition including CYP3A4, CYP3A5, SLCO1B3 (OATP8), and ABCB1 (MDR1) and paclitaxel pharmacokinetic parameters and toxicity after one course of treatment.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) IV over 30 minutes on days 1, 8, 15, 22, 29, 36, 43, and 50. Treatment may repeat off study every 9 weeks in the absence of disease progression or unacceptable toxicity.

Serial blood samplings are obtained at specified time points during course 1 including baseline and days 1 and 8 of course 1 for pharmacokinetic studies. Samples are also examined for genotype by PCR including variant genotypes in 2C8, CYP3A4, CYP3A5, ABCB1, ABCC2, ABCC10 and OATP1B3 genes.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Patients must have an incurable advanced or refractory tumor amenable to treatment with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel)

    • Per the National Comprehensive Cancer Network, the following cancer sites have been shown to be responsive to taxane therapy:

      • Prostate cancer
      • Breast cancer
      • Non-small cell lung cancer
      • Bladder cancer
      • Head and neck cancer
      • Oral cancer
      • Cervical cancer
      • Ovarian cancer
      • Endometrial cancer
      • Esophageal cancer
      • Gastric cancer
      • Germ cell tumors
      • Tumors of unknown primary
      • Soft tissue sarcomas
      • Small cell lung cancer
      • Testicular cancer
      • Upper genitourinary tract cancers

PATIENT CHARACTERISTICS:

  • Patients must have performance status 0-2 by the ECOG scale
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ institutional upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN (if bone metastasis is present in the absence of liver metastasis, alkaline phosphatase must be ≤ 5 x ULN)
  • Creatinine ≤ 1.5 x ULN
  • Patients must not have baseline sensory neuropathy ≥ grade 2
  • Women must not be pregnant or breastfeeding
  • Negative blood or urine pregnancy test
  • Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception

PRIOR CONCURRENT THERAPY:

  • Prior treatment is allowed, which may include prior taxane therapy

    • If patient has had prior therapy(ies), s/he must have received last treatment ≥ 28 days prior to registration
  • Patients must not be receiving colony stimulating factors (CSFs)

    • Previous CSFs must have been discontinued > 14 days prior to registration
  • Patients must not be receiving concomitant treatment with any of the following (prior use is allowed, but must have been discontinued ≥ 28 days prior to registration):

    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Rifampicin
    • Phenobarbital
    • Hypericum perforatum (St. John's wort)
    • Ketoconazole
  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: NCT00499291

Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Sridhar Mani, MD Albert Einstein College of Medicine of Yeshiva University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00499291     History of Changes
Other Study ID Numbers: CDR0000554709, ECOG-E1Y06
Study First Received: July 10, 2007
Last Updated: September 25, 2008
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
recurrent bladder cancer
stage III bladder cancer
stage IV bladder cancer
recurrent renal cell cancer
stage III renal cell cancer
stage IV renal cell cancer
clear cell sarcoma of the kidney
rhabdoid tumor of the kidney
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
recurrent cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
recurrent endometrial carcinoma
stage III endometrial carcinoma

Additional relevant MeSH terms:
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014