Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation

NCT00858403 | Terminated Phase 2 Results DMC

• 2 other identifiers: MCC-15656CA180214
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to learn how patients with Advanced Non-Small Cell Lung Cancer (NSCLC) respond to the study drug Dasatinib. The study drug, Dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. The use of Dasatinib in this study is considered experimental.

Conditions

Lung Cancer

Keywords

Advanced Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participant Progressors vs. Non-progressors With Tumor Response

  We planned to assess whether the extent of inhibition of extracellular signal-regulated protein kinase (ERK) phosphorylation in lung cancer cells exposed ex vivo to dasatinib significantly differed between patients categorized as progressors or non-progressors through standard Response Evaluation Criteria In Solid Tumors (RECIST)

  1 year, 4 months

Secondary Outcomes (6)

• Number of Participants With Response to Dasatinib

  1 year, 4 months

• Number of Participants With Progression Free Survival (PFS) at 6 Months

  1 year, 4 months

• Number of Participants With Serious Adverse Events (SAEs)

  1 year, 4 months

• Number of Participant Progressors vs. Non-Progressors With Inhibition Response

  1 year, 4 months

• Correlation Between Extent of Inhibition and Concentration of Dasatinib

  1 year, 4 months

Study Arms (1)

Treatment with Dasatinib

EXPERIMENTAL

Dasatinib 140 mg orally (po) every day starting Day #1, continuous dosing. This dose was chosen based on the current experience in patients with solids tumors who have had prior chemotherapy.

Drug: Dasatinib

Interventions

Dasatinib DRUG

Take tablets of Dasatinib by mouth once a day.

Also known as: SPRYCEL®

Treatment with Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented diagnosis of NSCLC that is advanced/metastatic (Stage IIIB/IV).
• Performance Status (ECOG) 0-2
• Previous chemotherapy with the exception of dasatinib. Patients who have had any type of previous chemotherapy regimens for non-small cell lung cancer are eligible.
• Adequate Organ Function:
• Total bilirubin \< 2.0 times the institutional Upper Limit of Normal (ULN)
• Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN
• Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN)
• Serum Creatinine \< 1.5 time the institutional ULN
• Hemoglobin, Neutrophil count, Platelets, prothrombin time (PT), partial thromboplastin time (PTT) all Grade 0-1
• Ability to take oral medication
• Concomitant Medications:
• Agree to discontinue St. Johns Wort while receiving dasatinib therapy
• Agree that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
• Women of childbearing potential (WOCBP):
• A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration

You may not qualify if:

• No malignancy \[other than the one treated in this study\] which required radiotherapy or systemic treatment within the past 5 years.
• Prior dasatinib therapy.
• Concurrent medical condition which may increase the risk of toxicity, including:
• Patients with severe pulmonary disease that increases the risk of toxicity related to dasatinib-induced pleural effusions. This includes chronic obstructive pulmonary disease or pleural effusions (malignant or benign) requiring chronic oxygen therapy or patients that have had prior pneumonectomy. Patients that have a pulmonary embolism and require oxygen therapy will be excluded but not those patients who have a pulmonary embolism but do not require oxygen therapy. Patients with active pleural effusions not controlled with pleurodesis will be excluded.
• Uncontrolled angina, congestive heart failure or MI within (6 months)
• Diagnosed congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
• Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
• Patients with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
• History of significant bleeding disorder unrelated to cancer, including:
• Diagnosed congenital bleeding disorders
• Diagnosed acquired bleeding disorder within one year
• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding
• Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
• quinidine, procainamide, disopyramide

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

The low accrual of 7 participants prevented us from completing the planned analysis. Target accrual was 40.

Results Point of Contact

• Title: Eric Haura, M.D., via Moffitt Cancer Center
• Organization: H. Lee Moffitt Cancer Center and Research Institute

eric.haura@moffitt.org

813-745-6827

Study Officials

• Eric Haura, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2009
• First Posted: March 9, 2009
• Study Start: March 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: January 15, 2014
• Results First Posted: September 7, 2011

Record last verified: 2013-12

Locations

US (1)