Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Greg Otterson

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Other: immunoenzyme technique; Genetic: protein expression analysis; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: carboplatin; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT00729612

OSU-08059

NCI-2011-03196 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well paclitaxel albumin-stabilized nanoparticle formulation given together with carboplatin works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Full description

OBJECTIVES:

Primary

• To determine the response rate, in terms of overall response rate (complete response and partial response), of paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in patients with stage IIIB-IV or recurrent non-small cell lung cancer who are ineligible for treatment with bevacizumab.

Secondary

• To evaluate safety of this regimen in these patients.
• To describe the overall survival of these patients.
• To describe progression-free survival of these patients.

Tertiary Objectives

• To explore, in a pilot fashion, the activity of this regimen using predictive biomarkers including serum SPARC levels, methylation of SPARC in primary tumor samples and serum, Ras mutations, ERCC1 and SPARC immunohistochemistry, and serum miRNA expression profiles.

OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 1-2 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Paraffin-embedded tissue blocks or unstained slides and blood samples are collected for correlative studies. Samples are analyzed for serum SPARC by ELISA, Ras mutations, ERCC1 AND SPARC by immunohistochemistry, and serum miRNA expression profiling.

After completion of study treatment, patients are followed periodically.

Enrollment: 63 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC) meeting 1 of the following criteria:

  • Stage IIIB disease with malignant pleural effusion
  • Stage IV disease
  • Recurrent disease

• Squamous cell histology allowed

• Not eligible for curative treatment or treatment with bevacizumab

• Measurable disease according to RECIST

• Tumor (paraffin blocks or slides) must be available for correlative biomarker studies

• No uncontrolled brain metastases (or leptomeningeal disease)

  • Controlled brain metastases allowed

    • Able to receive appropriate therapeutic radiotherapy
    • Able to taper off all steroids without symptoms suggestive of increased intracranial pressure (nausea, vomiting, focal neurologic symptoms) for at least 7 days

PATIENT CHARACTERISTICS:

• ECOG (Eastern Cooperative Oncology Group) performance status 0-2

• ANC (absolute neutrophil count) ≥ 1.5 x 10^9/L

• Platelets ≥ 100 x 10^9/L

• Hemoglobin ≥ 9.0 g/L

• Total bilirubin ≤ 1.5 mg/dL

• AST (aspartate aminotransferase) and ALT (alanine aminotransferase) < 2.5 times upper limit of normal

• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 mg/mL

• No known HIV or hepatitis B or C

• Not pregnant

• Negative pregnancy test

• Thrombotic or embolic event within the past 6 months allowed, provided adequately controlled with therapeutic anticoagulation

• Hemoptysis allowed, provided it is not life threatening or requires palliative procedures (e.g., endobronchial therapy or radiotherapy)

• No cardiac disease, including any of the following:

  • NYHA (New York Heart Association) class III-IV congestive heart failure
  • Unstable angina (angina symptoms at rest)
  • New onset angina (began within the past 3 months)
  • Myocardial infarction within the past 6 months

• No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal medical management

• No peripheral neuropathy ≥ grade 2

• No active clinically serious infection > CTCAE grade 2

• No serious non-healing wound, ulcer, or bone fracture

• No significant traumatic injury within the past 4 weeks

• No evidence or history of bleeding diathesis or coagulopathy

• No prior malignancy, except for adequately treated basal cell skin cancer, carcinoma in situ of the cervix, or other cancer for which the patient has been disease-free for 2 years

  • Stage I (T1c) prostate cancer adequately treated 2 years prior to diagnosis of NSCLC allowed, however metastatic prostate cancer currently receiving hormonal therapy or chemotherapy is not allowed

• No significant psychiatric illness, in the opinion of the principal investigator, that would prevent adequate informed consent or render therapy unsafe

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent therapeutic anticoagulation, > 325 mg acetylsalicylic acid, or chronic non-steroid anti-inflammatory drug use allowed
• At least 14 days since prior and no concurrent radiotherapy
• More than 4 weeks since prior major surgery or open biopsy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 1 patient group

Treatment (nab-paclitaxel, carboplatin)

Experimental group

Description:

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 1-2 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: paclitaxel albumin-stabilized nanoparticle formulation

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Other: immunoenzyme technique

Drug: carboplatin

Genetic: protein expression analysis