AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer

Phase 2

Completed

Conditions: Malignant Pleural Effusion
Extensive Stage Small Cell Lung Cancer
Recurrent Small Cell Lung Cancer
Lung Metastases

Interventions: Drug: saracatinib

Registration Number: NCT00528645

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II study is studying how well giving AZD0530 works in treating patients with extensive-stage small cell lung cancer.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the 12-week progression-free survival rate of patients with extensive stage small cell lung cancer treated with AZD0530.

SECONDARY OBJECTIVES:

I. To determine the response rate in patients treated with this drug. II. To determine the overall survival and time-to-progression in patients treated with this drug.

III. To determine the adverse events of AZD0530 in these patients IV. To determine the effect of AZD0530 treatment on levels of circulating tumor cells in these patients.

V. To determine potential predictive markers of response in circulating tumor cells after treatment with this drug.

VI. To evaluate the rate of tumor marker (i.e., circulating tumor cells) stabilization in patients treated with this drug.

TERTIARY OBJECTIVES:

I. To determine the effect of AZD0530 treatment on levels of circulating tumor cells.

II. To determine potential predictive markers of response in circulating tumor cells after treatment with this drug.

III. To evaluate the rate of tumor marker (i.e., circulating tumor cells) stabilization in patients treated with this drug.

OUTLINE: Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are obtained at baseline and periodically during study to determine levels of circulating tumor cells for defined translational studies.

After completion of study therapy, patients are followed periodically for up to 2 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Histologically or cytologically confirmed small cell lung cancer
- No mixed histology
Extensive stage disease, defined as any of the following:
- Metastatic disease outside the chest
- Contralateral supraclavicular nodes or contralateral hilar nodes that cannot be included in a single radiation port
- Cytologically confirmed malignant pleural effusion
  - Clinically significant effusions (e.g., symptomatic pleural effusion) must be drained prior to treatment
Previously untreated disease* OR stable disease, partial response, or complete response ≤ 4 weeks after completion of one course (four 3-week courses) of standard platinum-based chemotherapy
No symptomatic, untreated, or uncontrolled CNS metastases
- CNS metastases previously treated with whole brain radiotherapy allowed
ECOG performance status (PS) 0-2
Life expectancy ≥ 12 weeks
WBC ≥ 3,000/mm³
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin > 9.0 g/dL
Total bilirubin < 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 3 times ULN
ALT and AST ≤ 3 times ULN (≤ 5 times ULN if liver involvement)
Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
Proteinuria ≤ +1 on two consecutive dipsticks taken no less than 24hours apart
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective protection during and for up to 8 weeks after completion of study therapy
QTc interval ≤ 460 msec
No seizure disorder
No significant traumatic injury ≤ 4 weeks prior to registration
No clinically significant infection
No HIV-positivity
No second primary malignancy, except for carcinoma in situ of the cervix or nonmelanoma skin cancer, unless prior malignancy was diagnosed and treated ≥ 5 years with no subsequent evidence of recurrence
- Patients with a history of low grade(Gleason score ≤ 6) localized prostate cancer will be eligible even if diagnosed < 5 years prior to registration
No concurrent severe and/or uncontrolled medical conditions, including any of the following:
- Cardiac arrhythmias
- Angina pectoris uncontrolled with medication
- Myocardial infarction within the past 3 months
- Significant ECG abnormalities
- Hypertension, labile hypertension, or history of poor compliance with anti-hypertensive medication
- Congestive heart failure within the past 3 months, unless ejection fraction > 40%
- Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the lung
- Poorly controlled diabetes
No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
No condition that impairs the ability to swallow AZD0530 tablets, including any of the following:
- Gastrointestinal tract disease resulting in an inability to take oral medication or requiring IV alimentation
- Prior surgical procedures affecting absorption of AZD0530 tablets
- Active peptic ulcer disease
No serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study
At least 4 weeks since prior major surgery (i.e., laparotomy) or open biopsy
At least 2 weeks since prior minor surgery
At least 4 weeks since any prior investigational ancillary therapy (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation)
At least 7 days since prior use of strong inhibitors of CYP3A4 and no concurrent use for up to 7 days after discontinuation of AZD0530
Prior nonthoracic palliative radiotherapy allowed
Concurrent bisphosphonates for treatment of lytic metastatic bone disease allowed at the discretion of the treating physician
No concurrent prophylactic granulocyte colony-stimulating factor (i.e., G-CSF)
No concurrent products that stimulate thrombopoiesis
No concurrent St. John's wort
No other concurrent chemotherapy, immunotherapy, hormonal therapy,or radiotherapy

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (saracatinib)	saracatinib	Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are obtained at baseline and periodically during study to determine levels of circulating tumor cells for defined translational studies.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival Rate at 12 Weeks	12 weeks	The progression-free survival (PFS) rate at 12 weeks will be estimated by calculating the number of patients that are alive and progression-free at 12 weeks post-registration divided by the total number of evaluable patients and multiplied by 100. All patients meeting the eligibility criteria who have signed a consent form, begun AZD0530 treatment, and are not lost to follow-up before 12 weeks, will be considered evaluable for the 12-week progression-free survival (PFS) rate. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is defined as having a new lesion or having at least a 20% increase in the sum of the longest diameter of target lesions from baseline.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From registration to death due to any cause, assessed up to 2 years	Overall Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart)	After every other 21-day cycle, up to 2 years.	Response was assessed using the RECIST v1.1 criteria. Patients were evaluated after every other cycle (after cycle 2, 4, 6, etc...) and when progression is suspected. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart..
Progression Free Survival	From registration to documentation of disease progression or death, assessed up to 2 years	Progression Free Survival (PFS) is defined as the time from registration to documentation of disease progression or death, whichever occurs first. The distribution of time to progression will be estimated using the method of Kaplan-Meier.