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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00499291
• Other study ID #: CDR0000554709
• Secondary ID: ECOG-E1Y06
• Status: Withdrawn
• Phase: N/A
• Start date: September 2006

Study information

• Verified date: May 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• paclitaxel albumin-stabilized nanoparticle formulation

Procedure:
• gene expression analysis

• laboratory biomarker analysis

• pharmacological study

• polymerase chain reaction

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inter-individual pharmacokinetic variability
Secondary	Pharmacokinetic parameters
Secondary	Neutropenia
Secondary	CYP2C8*3 variant expression
Secondary	Genetic variance relating to pharmacokinetics and toxicity