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 has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00638937
First received: March 18, 2008
Last updated: October 7, 2013
Last verified: October 2013
  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:


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.


Enrollment: 32
Study Start Date: February 2008
Primary Completion Date: June 2013 (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: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the rate of disease control (i.e., lack of disease progression, a combined rate of objective complete and partial response, and stable disease) for at least 4 cycles of therapy in patients with AZD0530 (saracatinib) in patients with advanced non-small cell lung cancer that had previously been treated with platinum-based combination chemotherapy.

SECONDARY OBJECTIVES:

I. To assess the objective response rate (complete and partial response), stable disease rate, duration of response or stable disease, progression-free, median and 6 month overall survival rates, safety and tolerability of this treatment.

TERTIARY OBJECTIVES:

I. To 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 disease progression or unacceptable toxicity.

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 vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (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:

  • Patients must have recurrent, metastatic or locally advanced unresectable, histologically or cytologically confirmed non-small cell lung cancer
  • Patients must have measurable disease, defined (per Response Evaluation Criteria In Solid Tumors [RECIST]) 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 computed tomography (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
    • Patients must not have had prior treatment with an epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor
    • Patients must have completed chemotherapy, surgery or radiotherapy at least 4 weeks before study entry and must have recovered from the toxic effects from any prior therapy
    • Patients must not have had more than 40% of their bone marrow radiated and must have either measurable disease outside the field or documented progression post radiation therapy
  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 OR Karnofsky >= 60%)
  • Leukocytes >= 3 x 10^9/L
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelet count >= 10 x 10^9/L
  • Hemoglobin > 9 g/dL (may be transfused to meet this)
  • Total bilirubin =< 1.5 times institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 times IULN (=< 5 times ULN in the presence of liver metastases)
  • Creatinine =< 1.5 times IULN OR creatinine clearance >= 50 mL/min/1.73 m^2
  • Urine protein creatinine (UPS) ratio =< 1.0 OR urine protein > 1.0, 24 hour urine for protein should be < 1000mg
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 8 weeks following cessation of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • No cytochrome P450 3A4 (CYP3A4)-active agents or substances is not permitted during protocol treatment, and patients who must continue treatment with these agents are not eligible; prohibited drugs should be discontinued seven (7) days prior to the administration of the first dose of AZD0530 and for 7 days following discontinuation of AZD0530
  • Patients may not be receiving any other investigational agents
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD0530 are not eligible
  • Patients with QTc prolongation (i.e., QTc interval >= 460 msec) or other significant electrocardiogram (ECG) abnormalities are ineligible
  • Patients with poorly controlled hypertension (i.e., systolic blood pressure [BP] of 140 mm Hg or higher, or diastolic BP of 90 mm Hg or higher) are ineligible
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow AZD0530 tablets are excluded
  • Patients with treated brain metastases which are clinically and radiologically stable are permitted; those requiring steroids or with neurological symptoms should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • Patients with intercurrent cardiac dysfunction including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia are excluded as are those with a history of ischemic heart disease including myocardial infarction
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because AZD0530 has the potential for teratogenic or abortifacient effects as shown by the gross fetal malformations and effects on embryofetal survival seen in reproductive toxicity studies in the rat; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD0530, breastfeeding should be discontinued if the mother is treated with AZD0530
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD0530; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Sponsors and Collaborators
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, NCI-2009-01053, PMH-PHLO-053, CDR0000587610, PHL-053, 7555, N01CM00032, N01CM62203
Study First Received: March 18, 2008
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Saracatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014