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

NCT00444015 | Completed Phase 1 DMC

• 2 other identifiers: MCC-14984BMS Protocol Number: CA180080
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

Erlotinib; Dasatinib; Epidermal growth factor receptor (EGFR); Tyrosine kinase; NSCLC; Pharmacokinetics (PK); Lung

Outcome Measures

Primary Outcomes (2)

• Number of Serious Adverse Events (SAEs) Reported

  Determine the safety and tolerability of erlotinib in combination with dasatinib in patients with advanced NSCLC

  3 months per patient

• Determine Maximum Tolerated Dose (MTD)

  Determine the MTD of erlotinib in combination with dasatinib and the phase II dose

  3 months per patient

Secondary Outcomes (4)

• Pharmacokinetics (PK)

  3 months per patient

• Changes in Serum Vascular Endothelial Growth Factor (VEGF) and Interleukin(IL)-8 Pre-treatment and Post-treatment

  3 months per patient

• Number of Participants With Complete Response (CR) and Partial Response (PR)

  3 to 6 months

• Number of Participants With Progression Free Survival (PFS)

  6 months

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Drug: Erlotinib in combination with Dasatinib

Interventions

Erlotinib in combination with Dasatinib DRUG

6 Cycles @ 28 Days

Also known as: Tarceva™, SPRYCEL®

Dose Escalation

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).
• 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.

You may not qualify if:

• 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.

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

Related Links

• Moffiitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Dasatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Pyrimidines

Study Officials

• Eric B. Haura, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2007
• First Posted: March 7, 2007
• Study Start: March 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: February 23, 2017

Record last verified: 2011-06

Locations

US (1)