AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00528645
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arm: 1
• Duration (Months): 66
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Extensive Stage Small Cell Lung Cancer; Lung Metastases; Malignant Pleural Effusion; Recurrent Small Cell Lung Cancer	Drug: saracatinib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

1. 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.

2. 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.

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

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

TERTIARY OBJECTIVES:

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

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

3. 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 Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Nov 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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..

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Central Cancer Treatment Group	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Julian Molina, North Central Cancer Treatment Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00528645
• Other Study ID Numbers: NCI-2012-01831; NCI-2012-01831; NCCTG-N0621; CDR0000563952; N0621; N0621; U10CA025224
• First Posted: Sep 12, 2007
• Last Update Posted: Dec 7, 2017
• Last Verified: Nov 1, 2017

• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Pleural Effusion, Malignant; Pleural Effusion; Saracatinib

Study Results

Participant Flow

Recruitment Details	24 patients were enrolled from 13 medical clinics from February 5, 2008 to August 21, 2008.
Pre-assignment Detail	One patient cancelled prior to treatment initiation and is excluded in the analysis.

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. saracatinib : saracatinib 175mg given orally daily with re-treatment every 3 weeks
Period Title: Overall Study
STARTED	23
COMPLETED	20
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	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. saracatinib : saracatinib 175mg given orally daily with re-treatment every 3 weeks
Overall Participants	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	14 60.9%
Male	9 39.1%
Region of Enrollment (participants) [Number]
United States	23 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Rate at 12 Weeks
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. saracatinib: saracatinib 175mg given orally daily with re-treatment every 3 weeks
Measure Participants	23
Number (95% Confidence Interval) [percentage of participants]	26 113%

2. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	From registration to death due to any cause, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	saracatinib : saracatinib 175mg given orally daily with re-treatment every 3 weeks
Measure Participants	23
Median (95% Confidence Interval) [months]	7.8

3. Secondary Outcome

Title	Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart)
Description	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..
Time Frame	After every other 21-day cycle, up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. saracatinib: saracatinib 175mg given orally daily with re-treatment every 3 weeks
Measure Participants	23
Complete Response (CR)	0 0%
Partial Response (PR)	0 0%

4. Secondary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	From registration to documentation of disease progression or death, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. saracatinib: saracatinib 175mg given orally daily with re-treatment every 3 weeks
Measure Participants	23
Median (95% Confidence Interval) [months]	1.5

Adverse Events

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	saracatinib : saracatinib 175mg given orally daily with re-treatment every 3 weeks
All Cause Mortality
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	6/23 (26.1%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/23 (4.3%)	1
Cardiac disorders
Atrial fibrillation	1/23 (4.3%)	1
Gastrointestinal disorders
Constipation	1/23 (4.3%)	1
Diarrhea	1/23 (4.3%)	1
Nausea	2/23 (8.7%)	2
Vomiting	2/23 (8.7%)	2
General disorders
Edema limbs	2/23 (8.7%)	2
Fatigue	1/23 (4.3%)	1
Infections and infestations
Pneumonia	1/23 (4.3%)	1
Investigations
Aspartate aminotransferase increased	1/23 (4.3%)	1
Bilirubin increased	1/23 (4.3%)	1
Leukocyte count decreased	1/23 (4.3%)	1
Platelet count decreased	3/23 (13%)	3
Metabolism and nutrition disorders
Anorexia	1/23 (4.3%)	1
Serum albumin decreased	1/23 (4.3%)	1
Serum calcium decreased	1/23 (4.3%)	1
Serum potassium decreased	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/23 (4.3%)	1
Dyspnea	2/23 (8.7%)	2
Hypoxia	1/23 (4.3%)	1
Pleural effusion	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	22/23 (95.7%)
Blood and lymphatic system disorders
Hemoglobin decreased	20/23 (87%)	39
Gastrointestinal disorders
Diarrhea	6/23 (26.1%)	26
Lower gastrointestinal hemorrhage	1/23 (4.3%)	1
Nausea	9/23 (39.1%)	12
Vomiting	7/23 (30.4%)	9
General disorders
Fatigue	16/23 (69.6%)	45
Fever	1/23 (4.3%)	1
Hepatobiliary disorders
Hepatic failure	1/23 (4.3%)	1
Infections and infestations
Bladder infection	1/23 (4.3%)	1
Skin infection	1/23 (4.3%)	1
Investigations
Alanine aminotransferase increased	1/23 (4.3%)	1
Alkaline phosphatase increased	1/23 (4.3%)	1
Aspartate aminotransferase increased	2/23 (8.7%)	2
Bilirubin increased	1/23 (4.3%)	1
Creatinine increased	8/23 (34.8%)	19
Laboratory test abnormal	1/23 (4.3%)	1
Leukocyte count decreased	5/23 (21.7%)	5
Neutrophil count decreased	1/23 (4.3%)	2
Platelet count decreased	7/23 (30.4%)	8
Weight loss	1/23 (4.3%)	1
Metabolism and nutrition disorders
Anorexia	4/23 (17.4%)	4
Blood glucose increased	3/23 (13%)	3
Serum albumin decreased	1/23 (4.3%)	1
Serum phosphate decreased	1/23 (4.3%)	1
Serum sodium decreased	2/23 (8.7%)	2
Musculoskeletal and connective tissue disorders
Bone pain	1/23 (4.3%)	1
Myalgia	5/23 (21.7%)	5
Nervous system disorders
Headache	2/23 (8.7%)	2
Taste alteration	2/23 (8.7%)	2
Renal and urinary disorders
Protein urine positive	6/23 (26.1%)	18
Respiratory, thoracic and mediastinal disorders
Respiratory tract hemorrhage	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	4/23 (17.4%)	6
Vascular disorders
Hot flashes	1/23 (4.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.