Phase II Study of Dasatinib in Previously Treated Patients With Advanced NSCLC

NCT00787267 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro00008303
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief Summary

On this study patients will receive dasatinib, a targeted therapy, for advanced NSCLC that has progressed after previous therapy. Safety and response to dasatinib will be assessed. Fresh frozen tumor tissue must be available for genomics analysis prior to initiating dasatinib therapy. A biopsy must be obtained after any prior chemotherapy. If fresh frozen tumor tissue is not available, a biopsy will be required to participate in this trial.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC; Lung Cancer; Dasatinib; Genomics; Genomics analysis; Genomic signature

Outcome Measures

Primary Outcomes (1)

• Tumor Response

  Tumor response rate was defined by RECIST criteria: CR (complete response) = disappearance of all target lesions taking as reference the baseline sum of the longest diameter (LD); PR (partial response) = at least a 30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease) = at least a 20% increase in the sum of the longest diameter of target lesions as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD (stable disease) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since the treatment started

  2 years

Secondary Outcomes (4)

• Overall Survival

  Progression and survival every 6 months

• Grade 3-5 Toxicity Associated With Dasatinib Treatment

  Duration of dasatinib treatment plus 30 days

• Describe Change in Serum Levels of C-terminal Cross-linked Collagen I Between Pre-treatment and 6 Weeks After Starting Dasatinib.

  2 years

• Determine Relationship Between K-ras Gene Mutation and Response to Dasatinib.

  2 years

Study Arms (1)

Dasatinib

EXPERIMENTAL

After a biopsy is done to obtain fresh frozen tumor tissue (Stage I), dasatinib is to be administered as an oral dose of 70 mg twice daily on a continuous basis for 6 weeks. Every 6 weeks radiologic exam will be done to assess response. Treatment will continue until progression of disease, intolerable toxicity or patient withdrawal. For Stage II, a biopsy to obtain fresh frozen tumor tissue will also be done. Depending on results from Stage I and results of biopsy, treatment with dasatinib will be determined.

Drug: Dasatinib

Interventions

Dasatinib DRUG

70 mg PO twice daily until progression. Re-assess radiographically every 6 weeks.

Also known as: Sprycel

Dasatinib

Eligibility Criteria

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

You may qualify if:

• Histological/cytological documented non-small cell lung cancer (NSCLC). Documentation of recurrence required if treated with surgical resection and/or external beam radiation therapy (XRT) with curative intent and now have recurrent disease.
• Fresh tissue biopsy material for genomics analysis prior to initiating dasatinib. If prior XRT, tissue biopsy must be outside XRT field. Biopsy must be after any prior chemotherapy.
• Prior treatment (tx) to include one of the following:
• At least 1 prior systemic regimen (IV or oral agent) for Stage IV NSCLC or for recurrent disease.
• Recurrence within 12 months after completion of systemic neoadjuvant/adjuvant chemotherapy for early stage NSCLC.
• Combined modality platinum-based tx for Stage III NSCLC.
• Prior XRT permitted if ≥1 week since completion, XRT must be \<25% of bone marrow reserve.
• At least one, non-radiated, measurable lesion (per RECIST).
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) 0-2.
• Adequate Organ Function:
• Total bilirubin \< Upper limit normal (ULN)
• Hepatic enzymes (AST, ALT) ≤2.5x ULN
• Serum creatinine \<1.5x ULN
• Hemoglobin ≥9 gm/dL

You may not qualify if:

• Previous or concomitant malignancy in past 2 years other than curatively treated carcinoma in situ of cervix, or basal cell/squamous cell carcinoma of the skin.
• Prior tx with dasatinib or other agents that inhibit Src.
• Evidence of symptomatic pleural effusions (grade 2) unless undergo therapeutic thoracentesis as part of non-study care. Successful pleurodesis allowed. Patients who require supplemental oxygen or with oxygen saturation on room air \<89% are not eligible. Pericardial effusions of any grade are not eligible.
• Untreated documented symptomatic central nervous system (CNS) metastases.
• Cardiac Symptoms:
• Uncontrolled angina, congestive heart failure(CHF)or myocardial infarction within 6 months
• Diagnosed congenital long QT syndrome
• Any h/o clinically significant ventricular arrhythmias
• Prolonged QT corrected (QTc) interval on pre-entry EKG (\>450 msec)
• Uncontrolled B/P as defined as \>160/90 on B/P therapy
• Hypokalemia or hypomagnesaemia if it cannot be corrected.
• H/o diagnosed congenital acquired bleeding disorders.
• Ongoing or recent (≤3 months) significant (≥grade 3) GI bleeding.
• Con Meds:
• Drugs having risk of causing Torsades de Pointes (must stop drug 7 days before dasatinib);

Sponsors & Collaborators

• Duke University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Durham VA Medical Center

Durham, North Carolina, 27705, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Duke Raleigh

Raleigh, North Carolina, 27609, United States

Location

Related Publications (1)

• Downward J. Cancer biology: signatures guide drug choice. Nature. 2006 Jan 19;439(7074):274-5. doi: 10.1038/439274a. No abstract available.

  PMID: 16421553 BACKGROUND

Related Links

• Clinical Trials at Duke Comprehensive Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; 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

Results Point of Contact

• Title: Michael Kelley , MD
• Organization: Duke University Medical Center

kelleym@duke.edu

919-286-0411

Study Officials

• Michael Kelley, MD

  Duke University

  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: November 6, 2008
• First Posted: November 7, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 30, 2016
• Results First Posted: January 1, 2015

Record last verified: 2016-05

Locations

US (3)