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AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy

Primary Purpose

Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
saracatinib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Recurrent/metastatic/locally advanced unresectable, histologically or cytologically confirmed NSCLC
  • Measurable disease defined (RECIST) as at least 1 lesion measured in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan

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

    • <=1 line of prior therapy
    • Not have had prior treatment with EGFR Tyrosine kinase inhibitor
    • Completed chemotherapy/surgery/radiotherapy 4 weeks before study entry and must have recovered from toxic effects of prior therapy
    • Had >40% of their bone marrow radiated and must have either measurable disease outside field/documented progression post radiation therapy
  • Life expectancy >3 months
  • ECOG performance status =<2 OR Karnofsky >=60%
  • Leukocytes >=3x10^9/L
  • Absolute neutrophil count >=1.5x10^9/L
  • Platelet count >=10x10^9/L
  • Hemoglobin >9g/dL (may be transfused to meet this)
  • Total bilirubin =<1.5 times institutional ULN (IULN)
  • AST/ALT =<2.5xIULN (=<5 times ULN in the presence of liver metastases)
  • Creatinine =<1.5xIULN OR creatinine clearance >=50 mL/min/1.73m^2
  • Urine protein creatinine ratio =<1.0 OR urine protein >1.0, 24 hour urine for protein should be <1000mg
  • Women of childbearing potential/men must use adequate contraception (hormonal/barrier method of birth control; abstinence) prior to study entry, for duration of study participation, and for 8 weeks following cessation of study therapy
  • Ability to understand/willingness to sign written informed consent

Exclusion Criteria:

  • Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas/mitomycin C) prior to study entry/not recovered from AEs due to agents administered > than 4 weeks earlier
  • No CYP3A4-active agents permitted during protocol treatment. Patients requiring treatment with these agents are not eligible; prohibited drugs should be discontinued 7 days before first dose of AZD0530 and for 7 days after discontinuation of AZD0530
  • Cannot receive other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical/biologic composition to AZD0530
  • QTc prolongation (i.e.QTc interval >=460 msec)/other significant ECG abnormalities
  • Poorly controlled hypertension (i.e.systolic BP of 140 mmHg or higher, diastolic BP of 90mm Hg or higher)
  • Any condition impairing ability to swallow AZD0530 tablets
  • Treated brain metastases which are clinically and radiologically stable are permitted; patients requiring steroids/with neurological symptoms should be excluded because of poor prognosis/often develop progressive neurologic dysfunction
  • Intercurrent cardiac dysfunction including but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia are excluded as are those with ischemic heart disease history including myocardial infarction
  • Uncontrolled intercurrent illness including but not limited to ongoing/active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women excluded because AZD0530 has potential teratogenic/abortifacient effects; because unknown but potential risks for AEs in nursing infants secondary to treatment of mother with AZD0530, breastfeeding should be discontinued if mother is treated with AZD0530
  • HIV-positive patients on combination antiretroviral therapy are ineligible because potential for PK interactions with AZD0530; these patients have increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Sites / Locations

  • Juravinski Cancer Centre at Hamilton Health Sciences
  • The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
  • University Health Network-Princess Margaret Hospital
  • McGill University Department of Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (saracatinib)

Arm Description

Patients receive saracatinib PO, at a dose of 175 mg QD on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression

Outcomes

Primary Outcome Measures

Rate of Disease Control (Freedom From Disease Progression)
Lack of disease progression, a combined rate of objective complete (disapprearance of all target lesions) and partial responses (>= 30% decrease in sum of longest diameter of target lesions) and stable disease as determined by Response Evaluation Criteria in Solid Tumours (RECIST 1.0) for at least 4 cycles (16 weeks) of therapy. 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)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR 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
Stabilization of disease for atleast 4 cycles, leading to disease control 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
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
The Kaplan-Meier method will be used.
Progression-free Survival
Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause The Kaplan-Meier method will be used.
Median Overall Survival
The Kaplan-Meier method will be used.
Overall Survival
One year overall survival rate The Kaplan-Meier method will be used.

Full Information

First Posted
March 18, 2008
Last Updated
July 31, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00638937
Brief Title
AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (saracatinib)
Arm Type
Experimental
Arm Description
Patients receive saracatinib PO, at a dose of 175 mg QD on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression
Intervention Type
Drug
Intervention Name(s)
saracatinib
Other Intervention Name(s)
AZD0530
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Rate of Disease Control (Freedom From Disease Progression)
Description
Lack of disease progression, a combined rate of objective complete (disapprearance of all target lesions) and partial responses (>= 30% decrease in sum of longest diameter of target lesions) and stable disease as determined by Response Evaluation Criteria in Solid Tumours (RECIST 1.0) for at least 4 cycles (16 weeks) of therapy. 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.
Time Frame
112 days
Secondary Outcome Measure Information:
Title
Objective Response Rate (Complete and Partial Response)
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR 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.
Time Frame
From the start of the treatment until the criteria for response are met
Title
Stable Disease Rate
Description
Stabilization of disease for atleast 4 cycles, leading to disease control 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.
Time Frame
From the start of the treatment until the criteria for progression are met, assessed up to 1 year
Title
Duration of Response or Stable Disease
Description
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.
Time Frame
From first response until the criteria for progression are met, assessed up to 1 year
Title
Median Progression-free Survival
Description
The Kaplan-Meier method will be used.
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
Title
Progression-free Survival
Description
Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause The Kaplan-Meier method will be used.
Time Frame
6 months
Title
Median Overall Survival
Description
The Kaplan-Meier method will be used.
Time Frame
Up to 1 year
Title
Overall Survival
Description
One year overall survival rate The Kaplan-Meier method will be used.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Recurrent/metastatic/locally advanced unresectable, histologically or cytologically confirmed NSCLC Measurable disease defined (RECIST) as at least 1 lesion measured in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan Previously treated with firstline platinum-based systemic chemotherapy for advanced disease AND had at least disease stabilization as best response to firstline therapy <=1 line of prior therapy Not have had prior treatment with EGFR Tyrosine kinase inhibitor Completed chemotherapy/surgery/radiotherapy 4 weeks before study entry and must have recovered from toxic effects of prior therapy Had >40% of their bone marrow radiated and must have either measurable disease outside field/documented progression post radiation therapy Life expectancy >3 months ECOG performance status =<2 OR Karnofsky >=60% Leukocytes >=3x10^9/L Absolute neutrophil count >=1.5x10^9/L Platelet count >=10x10^9/L Hemoglobin >9g/dL (may be transfused to meet this) Total bilirubin =<1.5 times institutional ULN (IULN) AST/ALT =<2.5xIULN (=<5 times ULN in the presence of liver metastases) Creatinine =<1.5xIULN OR creatinine clearance >=50 mL/min/1.73m^2 Urine protein creatinine ratio =<1.0 OR urine protein >1.0, 24 hour urine for protein should be <1000mg Women of childbearing potential/men must use adequate contraception (hormonal/barrier method of birth control; abstinence) prior to study entry, for duration of study participation, and for 8 weeks following cessation of study therapy Ability to understand/willingness to sign written informed consent Exclusion Criteria: Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas/mitomycin C) prior to study entry/not recovered from AEs due to agents administered > than 4 weeks earlier No CYP3A4-active agents permitted during protocol treatment. Patients requiring treatment with these agents are not eligible; prohibited drugs should be discontinued 7 days before first dose of AZD0530 and for 7 days after discontinuation of AZD0530 Cannot receive other investigational agents History of allergic reactions attributed to compounds of similar chemical/biologic composition to AZD0530 QTc prolongation (i.e.QTc interval >=460 msec)/other significant ECG abnormalities Poorly controlled hypertension (i.e.systolic BP of 140 mmHg or higher, diastolic BP of 90mm Hg or higher) Any condition impairing ability to swallow AZD0530 tablets Treated brain metastases which are clinically and radiologically stable are permitted; patients requiring steroids/with neurological symptoms should be excluded because of poor prognosis/often develop progressive neurologic dysfunction Intercurrent cardiac dysfunction including but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia are excluded as are those with ischemic heart disease history including myocardial infarction Uncontrolled intercurrent illness including but not limited to ongoing/active infection or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women excluded because AZD0530 has potential teratogenic/abortifacient effects; because unknown but potential risks for AEs in nursing infants secondary to treatment of mother with AZD0530, breastfeeding should be discontinued if mother is treated with AZD0530 HIV-positive patients on combination antiretroviral therapy are ineligible because potential for PK interactions with AZD0530; these patients have increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Laurie
Organizational Affiliation
University Health Network-Princess Margaret Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
McGill University Department of Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy

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