AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer

Phase II Study of the c-SRC Inhibitor AZD0530 After Four Cycles of Cytoreductive Chemotherapy for Patients With Extensive Stage Small Cell Lung Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Lung Metastases; Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Malignant Pleural Effusion
• Intervention / Treatment: Drug: saracatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (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.	Drug: saracatinib; Given orally; Other Names: AZD0530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Rate at 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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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.	From registration to death due to any cause, assessed up to 2 years
Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart)	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..	After every other 21-day cycle, up to 2 years.
Progression Free Survival	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.	From registration to documentation of disease progression or death, assessed up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Julian Molina, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: September 10, 2007
• First Submitted That Met QC Criteria: September 10, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: November 2, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pleural Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Pleural Effusion, Malignant; Pleural Effusion; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Saracatinib
• Other Study ID Numbers: NCI-2012-01831 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA025224 (U.S. NIH Grant/Contract); NCCTG-N0621; CDR0000563952; N0621 (Other Identifier: CTEP)