Dasatinib in Treating Patients With Relapsed Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00470054
• Recruitment Status: Completed
• First Posted: May 7, 2007
• Results First Posted: April 26, 2013
• Last Update Posted: May 5, 2015
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

Brief Summary:

This phase II trial is studying how well dasatinib works in treating patients with relapse small cell lung cancer. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease	Intervention/treatment	Phase
Extensive Stage Small Cell Lung Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer	Drug: dasatinib	Phase 2

Detailed Description:

PRIMARY OBJECTIVE I. Determine the efficacy of dasatinib in patients with relapsed small cell lung cancer.

SECONDARY OBJECTIVE II. Determine the objective response rate (complete and partial response) in patients treated with this drug.

III. Determine the overall survival of patients treated with this drug. IV. Determine the toxicity of this drug in these patients.

OUTLINE:

Patients receive oral dasatinib twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least every 3 months for 1 year and then every 6 months for 3 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Dasatinib (NSC #732517) in Patients With Chemo-Sensitive Relapsed Small Cell Lung Cancer
• Study Start Date: April 2007
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: April 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment (dasatinib); Patients receive oral dasatinib twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: dasatinib; Given PO; Other Names: BMS-354825; Sprycel

Outcome Measures

Primary Outcome Measures :

1. 6 Week Progression Free Survival [ Time Frame: 6 weeks ]

   Percentage of patients who were alive and progression free at 6-weeks. The 6-week progression free survival was estimated using the Kaplan Meier method.

   Progressive Disease was defined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria as 20% increase in sum of longest diameter of target lesions.

Secondary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Time from registration to progression (up to 3 years) ]

   PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method.

   Progression is defined as in the primary outcome measure.

2. Response to Therapy [ Time Frame: Assessed every 2 cycles (up to 3 years) ]

   Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:

   • Complete Response (CR): disappearance of all target lesions;
   • Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
   • Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions;
   • Stable Disease (SD): small changes that do not meet above criteria.
3. Overall Survival [ Time Frame: Time from registration to death (up to 3 years) ]
   Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
4. Number of Participants With Grade 3 or Higher Adverse Events [ Time Frame: Assessed during treatment ]

   The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 was used to evaluate toxicity.

   Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer (SCLC) (limited or extensive stage disease)
• Progressive or recurrent disease after an initial response to first-line treatment with a platinum-based chemotherapy with or without concurrent definitive radiotherapy to the chest (chemotherapy must have been completed at least 90 days prior to documentation of relapse)
• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan

• Lesions that are not considered measurable include the following:

  • Bone lesions
  • Leptomeningeal disease
  • Ascites
  • Pleural or pericardial effusion
  • Abdominal masses that are not confirmed and followed by imaging techniques
  • Cystic lesions
  • Tumor lesions situated in a previously irradiated area, unless progression after radiotherapy is documented in these lesions
• No known brain metastases (previously treated brain metastases allowed provided they are neurologically stable for >= 4 weeks)
• ECOG performance status 0-1
• Platelet count >= 100,000/mm^3
• Bilirubin =< 1.5 times upper limit of normal (ULN)
• Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min
• AST =< 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test

• No significant cardiac disease, including any of the following:

  • New York Heart Association class III-IV heart disease
  • Myocardial infarction or ventricular tachyarrhythmia within the past 6 months
  • Prolonged QTc > 480 msec (Fridericia correction)
  • Major conduction abnormality (unless a cardiac pacemaker is present)
• No more than 1 prior chemotherapy regimen
• No prior dasatinib or compounds of similar chemical composition or similar biologic therapeutic activity including, but not limited to, any inhibitors of SRC, BCR-ABL, c-KIT, EPHA2, or PDGFRB kinases
• At least 2 weeks since prior definitive or palliative radiotherapy (prior radiotherapy allowed in the context of combined modality treatment with curative intent for limited stage disease; prophylactic cranial radiotherapy; or palliative radiotherapy initially or at relapse)
• At least 2 weeks since prior surgery and recovered
• At least 1 week since prior and no concurrent agents with proarrhythmic potential
• At least 1 week since prior and no concurrent CYP3A4 inhibitors or inducers
• At least 1 week since prior and no concurrent grapefruit concentrate
• No concurrent palliative radiotherapy
• No concurrent hormones or other chemotherapeutic agents, except steroids for adrenal failure, hormones for noncancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent chemotherapeutic or investigational agents
• Fertile patients must use effective contraception during and for >= 6 weeks after completion of study therapy

Contacts and Locations

Locations

United States, Illinois

Cancer and Leukemia Group B

Chicago, Illinois, United States, 60606

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Antonius Miller; Cancer and Leukemia Group B

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00470054
• Other Study ID Numbers: NCI-2009-00467; NCI-2009-00467 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000543528; CALGB 30602 ( Other Identifier: Cancer and Leukemia Group B ); CALGB-30602 ( Other Identifier: CTEP ); P30CA014236 ( U.S. NIH Grant/Contract ); U10CA031946 ( U.S. NIH Grant/Contract )
• First Posted: May 7, 2007
• Results First Posted: April 26, 2013
• Last Update Posted: May 5, 2015
• Last Verified: June 2014

Additional relevant MeSH terms:

Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Dasatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action