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Saracatinib in Treating Patients With Recurrent, Stage IIIB or Stage IV Non-Small Cell Lung Cancer Previously Treated With Combination Chemotherapy That Included Cisplatin or Carboplatin

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00638937
First received: March 18, 2008
Last updated: May 3, 2013
Last verified: April 2013
History of Changes
  Purpose

This phase II trial is studying how well saracatinib works in treating patients with recurrent, stage IIIB or stage IV non-small cell lung cancer previously treated with combination chemotherapy that included cisplatin or carboplatin. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
 Drug: saracatinib
Other: laboratory biomarker analysis
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD0530 in Patients With Advanced, Recurrent Non-Small Cell Lung Cancer Who Have Previously Received Platinum-Based Combination Chemotherapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Rate of disease control (freedom from disease progression) [ Time Frame: 112 days ] [ Designated as safety issue: No ]
    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.


Secondary Outcome Measures:
  • Objective response rate (complete and partial response) [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 1 year ] [ Designated as safety issue: No ]
    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.

  • Stable disease rate [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 1 year ] [ Designated as safety issue: No ]
    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.

  • Duration of response or stable disease [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 1 year ] [ Designated as safety issue: No ]
    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.

  • Median progression-free survival [ Time Frame: From the date of study enrollment to the time the criteria for disease progression are met, death or last contact, or the last tumor assessment before the initiation of further anticancer therapy, assessed up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Median overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Safety and tolerability of the treatment assessed using NCI CTCAE version 3.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.


Estimated Enrollment: 32
Study Start Date: February 2008
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (saracatinib)
Patients receive saracatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression
 Drug: saracatinib
Given PO
Other Name: AZD0530
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the rate of disease control (i.e., lack of disease progression, objective complete and partial response, and stable disease) in patients with recurrent, stage IIIB or IV non-small cell lung cancer treated with AZD0530 (saracatinib).

SECONDARY OBJECTIVES:

I. Assess the objective response rate (complete and partial response), stable disease rate, and duration of response or stable disease in patients treated with AZD0530.

II. Assess the progression-free, median, and 6-month overall survival rates in patients treated with AZD0530.

III. Assess the safety and tolerability of AZD0530 in these patients. IV. Evaluate potential predictive markers by assessing pretreatment intratumoral levels of src, Y419 phospho-src (P-Src), and c-terminal src kinase (Csk) in archival tumor biopsies.

OUTLINE: This is a multicenter study.

Patients receive saracatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Tumor tissue samples are collected at baseline and at 2 weeks after beginning treatment and are analyzed for c-Src protein expression and activity by immunofluorescence staining. P-glycoprotein levels and phosphorylation of focal adhesion kinase (FAK), paxillin, caveolin, and Stat-3 are also measured using tumor tissue samples. Blood samples are also used to measure levels of VEGF by ELISA.

After completion of study treatment, patients are followed every 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed non-small cell lung cancer, meeting both of the following criteria:

    • Locally advanced or metastatic (stage IIIB or IV) disease
    • Recurrent, unresectable disease
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan

  • Previously treated with first-line platinum-based systemic chemotherapy for advanced disease AND had at least stabilization of disease as best response to first-line therapy

    • No more than one line of prior therapy
  • Previously treated brain metastases allowed provided they are clinically and radiologically stable and there are no neurological symptoms or requirement for steroids
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • Platelet count ≥ 100,000/mm³
  • Leukocytes ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Hemoglobin > 9 g/dL (transfusion allowed)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
  • Urine protein creatinine ratio ≤ 1.0 OR urine protein < 1,000 mg by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 8 weeks after completion of study treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD0530
  • No QTc prolongation (i.e., QTc interval ≥ 460 msec) or other significant ECG abnormalities

  • No cardiac dysfunction including, but not limited to, the following:

    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • History of ischemic heart disease, including myocardial infarction
  • No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
  • No condition that would impair the ability to swallow AZD0530 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, or active peptic ulcer disease)
  • No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgery and recovered
  • Prior radiotherapy to target lesions allowed provided there is disease progression
  • No prior radiotherapy to > 40% of bone marrow
  • No prior EGFR tyrosine kinase inhibitors
  • No prior surgical procedures affecting absorption

  • No CYP3A4-active agents or substances for 7 days prior to, during, and for 7 days after completion of study treatment, including any of the following:

    • Ketoconazole
    • Itraconazole
    • Ritonavir
    • Mibefradil
    • Clarithromycin
    • Saquinavir
    • Indinavir
    • Erythromycin
    • Nefazadone
    • Fluconazole
    • Diltiazem
    • Alfentanil
    • Carbamazepine
    • Cyclosporine
    • Tacrolimus
    • Lovastatin
    • Simvastatin
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00638937

Locations
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
Ottawa, Ontario, Canada, K1Y 4E9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University Department of Oncology
Montreal, Quebec, Canada, H2W 1S6
Royal Victoria Hospital
Montreal, Quebec, Canada, H3A 1A1
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Scott Laurie University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00638937     History of Changes
Other Study ID Numbers: NCI-2009-01053, PHL-053, PMH-PHLO-053, CDR0000587610, N01CM62203, N01CM00032
Study First Received: March 18, 2008
Last Updated: May 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
 Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 23, 2013