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Phase I Study of Cetuximan Plus Dasatinib (BMS-354825) in Advanced Solid Malignancies

Phase 1
18 Years
Open (Enrolling)
Malignant Solid Tumour

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Trial Information

Phase I Study of Cetuximan Plus Dasatinib (BMS-354825) in Advanced Solid Malignancies

This is an open-label, phase I study of cetuximab and differing dose levels of dasatinib in
adult patients with advanced solid malignancies. Cetuximab will be administered as an
intravenous infusion on a standard dose and schedule (weekly, with the first dose at 400
mg/m2 and all subsequent weekly doses at 250 mg/m2). Dasatinib will be administered orally
on a continuous schedule at the following dose levels: 100 mg QD (once a day), 150 mg QD,
and 200 mg QD. Three to six patients will be enrolled at each dose level, and the final
recommended phase II cohort will be expanded to include up to 12 additional patients. The
doses will be escalated in successive cohorts of patients. On cycle 1, dasatinib
administration will start one day prior to cetuximab administration. One cycle will be
defined as 21 days, and cycles will continue until progression of disease or intolerable
toxicities occur. Peripheral blood samples and pharmacokinetic blood samples will be taken
on days 0, 1, 15, and 16 of Cycle 1 only. In patients with accessible tumor that give
consent, patients will undergo a baseline tumor biopsy and a repeat biopsy after 14-21 days
of the first cycle.

Inclusion Criteria:

1. Histologically or cytologically confirmed solid malignancy which is recurrent or
metastatic or resistant to therapy. Patients w/plan of surgery for recurrent disease
post cetuximab/dasatinib are eligible providing that they receive at least 2 cycles
of therapy and provide baseline and post-treatment tumor tissue for correlatives.

2. Any number of prior regimens but no prior EGFR or src inhibitors.

3. Age greater or equal to 18 years.

4. ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to

5. Life expectancy greater than 12 weeks.

6. Patients must have normal organ and marrow function:

- leukocytes greater than or equal to 3,000/mcL

- absolute neutrophil count greater than or equal to 1,500/mcL

- platelets greater than or equal to 100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of

- creatinine up to 1.5 x normal institutional limits

7. Ability to understand and the willingness to sign a written informed Consent

8. No concomitant medication that are CYP3A4 inducers or potent inhibitors and should
not take proton pump inhibitors and H2 antagonists in the first cycle of therapy and
should try to avoid taking proton pump inhibitors and H2 antagonists during rest of
treatment period.

9. Sexually active women of childbearing potential must use an effective method of birth
control during the course of the study, in a manner such that risk of failure is
minimized. All WOCBP must have a negative pregnancy test prior to first receiving
investigational product.

Exclusion Criteria:

1. Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C)
prior to entering study or those who have not recovered from adverse events due to
agents administered more than 4 weeks earlier.

2. Any other concurrent investigational agents.

3. Patients w/ untreated brain metastases. However, patients who have stable brain
disease (should be off corticosteroids) at least 4 weeks after completion of
appropriate therapy are eligible.

4. History of allergic reaction to monoclonal antibodies.

5. Inability to swallow oral medications unless patients use a feeding tube.

6. Uncontrolled angina or hypertension or any history of clinically significant
ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation,
or Torsades de pointes).

7. Prolonged QTc interval on pre-entry electrocardiogram (greater than 450 msec) on both
the Fridericia and Bazett's correction.

8. Diagnosed or suspected congenital long QT syndrome.

9. 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, lidoflazine.

10. Any other uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, symptomatic congestive heart failure, or psychiatric illness/social
situations that would limit compliance with study requirements.

11. 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).

12. HIV-positive patients receiving combination antiretroviral therapy.

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors

Outcome Time Frame:

Anticipated completion date December 2008

Safety Issue:


Principal Investigator

Edward Chu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Institutional Review Board

Study ID:




Start Date:

June 2007

Completion Date:

December 2012

Related Keywords:

  • Malignant Solid Tumour
  • advanced cancer
  • solid tumor
  • solid malignancies
  • phase I
  • Neoplasms



University of Pittsburgh Cancer Institute - Hillman Cancer Center Pittsburgh, Pennsylvania  15232