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

May 23, 2023 updated by: Eastern Cooperative Oncology Group

Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study of Nab-Paclitaxel (Nanoparticle Albumin Bound-Paclitaxel) in Patients With Advanced Solid Tumors

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Inter-individual pharmacokinetic variability

Secondary Outcome Measures

Outcome Measure
Pharmacokinetic parameters
Neutropenia
CYP2C8*3 variant expression
Genetic variance relating to pharmacokinetics and toxicity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eastern Cooperative Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Sridhar Mani, MD, Albert Einstein College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion

October 1, 2007

Study Completion

December 7, 2022

Study Registration Dates

First Submitted

July 10, 2007

First Submitted That Met QC Criteria

July 10, 2007

First Posted (Estimated)

July 11, 2007

Study Record Updates

Last Update Posted (Actual)

May 25, 2023

Last Update Submitted That Met QC Criteria

May 23, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000554709
  • ECOG-E1Y06

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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