Clinical trial NCT00499291: Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced or Refractory Solid Tumors
Official title: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study of Nab-Paclitaxel (Nanoparticle Albumin Bound-Paclitaxel) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Cancer
Keywords: 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
stage IV endometrial carcinoma
fallopian tube cancer
recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
ovarian sarcoma
ovarian stromal cancer
recurrent uterine sarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
recurrent hypopharyngeal cancer
stage III hypopharyngeal cancer
stage IV hypopharyngeal cancer
recurrent laryngeal cancer
stage III laryngeal cancer
stage IV laryngeal cancer
recurrent lip and oral cavity cancer
stage III lip and oral cavity cancer
stage IV lip and oral cavity cancer
recurrent metastatic squamous neck cancer with occult primary
untreated metastatic squamous neck cancer with occult primary
recurrent nasopharyngeal cancer
stage III nasopharyngeal cancer
stage IV nasopharyngeal cancer
recurrent oropharyngeal cancer
stage III oropharyngeal cancer
stage IV oropharyngeal cancer
recurrent paranasal sinus and nasal cavity cancer
stage III paranasal sinus and nasal cavity cancer
stage IV paranasal sinus and nasal cavity cancer
recurrent salivary gland cancer
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
recurrent gastric cancer
stage III gastric cancer
stage IV gastric cancer
adult central nervous system germ cell tumor
adult teratoma
ovarian teratoma
testicular teratoma
recurrent adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
recurrent carcinoma of unknown primary
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-07-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Inter-individual pharmacokinetic variability
Secondary outcomes:
measure: Pharmacokinetic parameters
measure: Neutropenia
measure: CYP2C8*3 variant expression
measure: Genetic variance relating to pharmacokinetics and toxicity
Other outcomes:
Locations:
Study officials:
affiliation: Albert Einstein College of Medicine
name: Sridhar Mani, MD
role: STUDY_CHAIR
References: