Clinical trial NCT00729612: Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official title: Phase II Trial of Abraxane Plus Carboplatin for Advanced NSCLC for Patients at Risk of Bleeding From VEGF Directed Therapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
squamous cell lung cancer
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Celgene Corporation
First posted: 2008-08-07
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria.
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 5 years
measure: Overall Survival
timeFrame: Up to 5 years
measure: Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Gregory A. Otterson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bertino EM, Williams TM, Nana-Sinkam SP, Shilo K, Chatterjee M, Mo X, Rahmani M, Phillips GS, Villalona-Calero MA, Otterson GA. Stromal Caveolin-1 Is Associated With Response and Survival in a Phase II Trial of nab-Paclitaxel With Carboplatin for Advanced NSCLC Patients. Clin Lung Cancer. 2015 Nov;16(6):466-74. doi: 10.1016/j.cllc.2015.05.004. Epub 2015 May 13.
citation: Owen DH, Williams TM, Bertino EM, Mo X, Webb A, Schweitzer C, Liu T, Roychowdhury S, Timmers CD, Otterson GA. Homologous recombination and DNA repair mutations in patients treated with carboplatin and nab-paclitaxel for metastatic non-small cell lung cancer. Lung Cancer. 2019 Aug;134:167-173. doi: 10.1016/j.lungcan.2019.06.017. Epub 2019 Jun 17.