Clinical trial NCT00528645: AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer
Official title: Phase II Study of the c-SRC Inhibitor AZD0530 After Four Cycles of Cytoreductive Chemotherapy for Patients With Extensive Stage Small Cell Lung Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Extensive Stage Small Cell Lung Cancer
Lung Metastases
Malignant Pleural Effusion
Recurrent Small Cell Lung Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-09-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival Rate at 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Overall Survival
timeFrame: From registration to death due to any cause, assessed up to 2 years
measure: Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart)
timeFrame: After every other 21-day cycle, up to 2 years.
measure: Progression Free Survival
timeFrame: From registration to documentation of disease progression or death, assessed up to 2 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: North Central Cancer Treatment Group
state: Minnesota
Study officials:
affiliation: North Central Cancer Treatment Group
name: Julian Molina
role: PRINCIPAL_INVESTIGATOR
References: