Phase I Dasatinib/Erlotinib in Recurrent Non-small Cell Lung Cancer (NSCLC)

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00444015
First received: March 5, 2007
Last updated: November 21, 2013
Last verified: June 2011
  Purpose

This is a single site phase I dose escalation trial of the epidermal growth factor receptor inhibitor Erlotinib with the SRC tyrosine kinase inhibitor Dasatinib in patients with previously treated advanced stage (Stage IIIB/IV disease) Non-Small Cell Lung Cancer (NSCLC). The treatment regimen consists of Erlotinib tablets starting Day 1 and Dasatinib tablets starting Day 9 for a 28-day cycle. If there are no Dose Limiting Toxicities (DLTs), dose escalation continues. The recommended phase II dose for this combined treatment will be defined and patients will be treated at the recommended phase II dose to confirm tolerability.


Condition Intervention Phase
Non-Small-Cell Lung Carcinoma
Drug: Erlotinib in combination with Dasatinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial Evaluating the Epidermal Growth Factor Receptor Inhibitor Erlotinib in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Recurrent Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Serious Adverse Events (SAEs) Reported [ Time Frame: 3 months per patient ] [ Designated as safety issue: Yes ]
    Determine the safety and tolerability of erlotinib in combination with dasatinib in patients with advanced NSCLC

  • Determine Maximum Tolerated Dose (MTD) [ Time Frame: 3 months per patient ] [ Designated as safety issue: No ]
    Determine the MTD of erlotinib in combination with dasatinib and the phase II dose


Secondary Outcome Measures:
  • Pharmacokinetics (PK) [ Time Frame: 3 months per patient ] [ Designated as safety issue: No ]
    Characterize the pharmacokinetics of the erlotinib/dasatinib combination

  • Changes in Serum Vascular Endothelial Growth Factor (VEGF) and Interleukin(IL)-8 Pre-treatment and Post-treatment [ Time Frame: 3 months per patient ] [ Designated as safety issue: No ]
    Assess serum angiogenic markers as pharmacodynamic markers of treatment

  • Number of Participants With Complete Response (CR) and Partial Response (PR) [ Time Frame: 3 to 6 months ] [ Designated as safety issue: No ]
    Estimate the objective response rate (CR and partial response PR). Partial Response is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Complete Response is defined as disappearance of all target lesions.

  • Number of Participants With Progression Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimate the 6-month progression free survival rate


Enrollment: 34
Study Start Date: March 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Drug: Erlotinib in combination with Dasatinib
6 Cycles @ 28 Days
Other Names:
  • Tarceva™
  • SPRYCEL®

Detailed Description:

This is a single site Phase I dose escalation trial of the epidermal growth factor receptor inhibitor Erlotinib with the SRC tyrosine kinase inhibitor Dasatinib in patients with previously treated advanced stage (Stage IIIB/IV disease) Non-Small Cell Lung Cancer (NSCLC). The screening evaluation will consist of a medical history including dates/description of your initial NSCLC diagnosis and documentation of any previous treatment. There will also be a physical examination including vital signs, height, weight, Eastern Cooperative Oncology Group (ECOG)performance status, blood draws for Complete Blood Count (CBC) and Complete Metabolic Panel (CMP) tests, neurological examination, a pregnancy test for female patients of childbearing potential, and (if applicable) any observable tumor measurements all within 14 days before study enrollment. A screening Electrocardiogram (EKG) as well as clinical testing to evaluate all known sites of malignant lesions, including Computed Tomography (CTs) of the chest and upper abdomen, the adrenal glands; ultrasound; or radionuclide scans of the bones; and/or other radiographic studies should be performed within 30 days prior to enrollment.

The treatment regimen consists of Erlotinib tablets starting Day 1 and Dasatinib tablets starting Day 9 for a 28-day cycle. If there are no DLTs, dose escalation continues. Patients continuing on therapy past two cycles will be seen by the treating physician every 4 weeks and will have complete History and Physical (H&P), CBC, and CMP. Tumor measurement and response assessment will occur every 6-8 weeks. Dasatinib and Erlotinib will be continued until progression of disease, unacceptable toxicity, or patient request.

The recommended phase II dose for this combined treatment will be defined and patients will be treated at the recommended phase II dose to confirm tolerability.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented diagnosis of NSCLC that is advanced/metastatic (Stage IIIB/IV).
  • Written informed consent.
  • The presence of progressive and measurable disease as defined by the -Response Evaluation Criteria in Solid Tumors (RECIST)
  • Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale
  • Have discontinued all previous systemic therapies for cancer, for at least 14 days prior to study entry and have had previous first line chemotherapy, have recovered from all acute effects of the therapies, and are considered for further chemotherapy, radiotherapy, or other investigational therapy after they have relapsed or progressed on previous treatment.
  • Exhibit patient compliance and geographic proximity that allow for adequate follow-up.
  • Adequate bone marrow reserve and organ function as follows:

    • Neutrophil count >1.5 x 10 to the 9th power/L and platelets > 100 x 10 to the 9th power/L.
    • Hepatic: total bilirubin less than or equal to 1.5 times upper limit of normal (ULN)
    • Alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN (or less than or equal to 5 times ULN in case of known liver involvement
    • Renal: Serum Creatinine less than or equal to 1.5 times upper limit of normal (ULN)
  • Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
  • At least 18 years of age.
  • Agrees to discontinue St. Johns Wort while receiving dasatinib therapy
  • Agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.

Exclusion Criteria:

  • Prior treatment with EGFR tyrosine kinase inhibitors or EGFR targeting agent
  • Have received treatment within the last 28 days with a drug that has not received regulatory approval for any indication at the time of study entry.
  • Have previously completed or withdrawn from this study or any other study investigating Dasatinib.
  • Pregnant or breastfeeding.
  • Documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
  • Serious concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator).
  • Uncorrected electrolyte disorder, including potassium <3.0 mEq/L).
  • Gastrointestinal disorder that in the opinion of the study physician may affect absorption of either erlotinib or dasatinib. This also includes the inability to swallow tablets.
  • Prior major surgery or radiation therapy within 14 days of initiation of treatment
  • Electrocardiogram (ECG) abnormalities indicative of cardiac disease (at the discretion of the investigator).
  • Uncontrolled angina, congestive heart failure or MI within six (6) months
  • Diagnosed or suspected congenital long QT syndrome
  • 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)
  • Uncontrolled hypertension.
  • History of significant bleeding disorder unrelated to cancer, including:

    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
    • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:

    • quinidine,
    • procainamide,
    • disopyramide,
    • amiodarone,
    • sotalol,
    • ibutilide,
    • dofetilide erythromycins,
    • clarithromycin,
    • chlorpromazine,
    • haloperidol,
    • mesoridazine,
    • thioridazine,
    • pimozide,
    • cisapride,
    • bepridil,
    • droperidol,
    • methadone,
    • arsenic,
    • chloroquine,
    • domperidone,
    • halofantrine,
    • levomethadyl,
    • pentamidine,
    • sparfloxacin; and
    • lidoflazine.
  • Patients with chronic obstructive pulmonary disease or pleural effusions (malignant or benign) requiring chronic oxygen therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00444015

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Eric B. Haura, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00444015     History of Changes
Other Study ID Numbers: MCC-14984, BMS Protocol Number: CA180080
Study First Received: March 5, 2007
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Erlotinib
Dasatinib
Epidermal growth factor receptor (EGFR)
Tyrosine kinase
NSCLC
Pharmacokinetics (PK)
Lung

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Mitogens
Erlotinib
Dasatinib
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014