Comparison of Biomarker Modulation by Inhibition of EGFR and/or SRC Family

• Status: Completed
• Trial end date: 2014-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The central hypothesis to be tested in this study is that dual blockade of EGFR and Src pathways or proteins are distinct compared to inhibition of either kinase alone in head and neck and lung cancers.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pittsburgh
• Treatments: Dasatinib; Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed, head and neck or lung cancers

• Any NSCLC histology is eligible. Stages I, II, IIIA (T3N1 only) or recurrent NSCLC that will be managed with surgery are eligible.

• Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) or lung site will be included.

• Surgical resection of head and neck or lung must be planned, either as primary treatment or salvage. Patients must have tissue available prior to receiving drug(s).

• Age greater then 18 years.

• ECOG performance status 0-2.

• Women of childbearing potential (WOCBP) must have:

1. A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration

2. Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped.

3. Ability to take oral medication (dasatinib must be swallowed whole).

4. Concomitant Medications

• Patients agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib).

• Patient agrees that IV biphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.

• Adequate hematologic, renal and hepatic function.

• Have signed written informed consent including a HIPPA form according to institutional guidelines.

Exclusion Criteria:

• Subjects who fail to meet the above criteria.

• Prior therapy for head and neck or lung cancers is allowed, with the exception of EGFR inhibitors. Any systemic therapy should have been completed at least 30 days prior to study enrollment.

• Pregnancy or breastfeeding. Women (patients or partners of male patients) of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy.

• Any unresolved chronic toxicity grade greater or equal to 2 from previous anticancer therapy (except alopecia and anemia).

• Acute hepatitis, known HIV, or active uncontrolled infection.

• Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.

• Prior treatment with an EGFR inhibitor (tyrosine kinase inhibitor).

• Cardiac Symptoms; any of the following should be considered for exclusion:

1. History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (Coumadin). Patients whose therapy is changed to heparin is eligible.

2. History of any other cancer except basal cell carcinoma of the skin.

3. Concurrent medical condition which may increase the risk of toxicity, including:

• Pleural or pericardial effusion of any grade

4. 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).

• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.

5. Concomitant Medications, any of the following should be considered for exclusion:

• 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)

6. Women who:

• are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug,

• have a positive pregnancy test at baseline, or

• are pregnant or breastfeeding.

7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.