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Phase I Trial of the Combination of Dasatinib and Lapatinib


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Trial of the Combination of Dasatinib and Lapatinib


OBJECTIVES:

- Determine the maximum tolerated dose of dasatinib combined with lapatinib ditosylate.

- Describe the toxicities associated with this treatment combination.

- Assess the pharmacokinetic interaction of lapatinib ditosylate and dasatinib.

- Assess the effect of the lapatinib ditosylate and dasatinib combination on circulating
tumor cells and on osteoclast precursor activation.

- Study the association of clinical (toxicity and/or tumor response or activity) with the
pharmacokinetic parameters, and/or biologic (pharmacodynamic) results.

- Describe the responses of this treatment combination.

OUTLINE: This is a multicenter study.

- Cohort I (determination of maximum tolerated dose [MTD]): Patients receive oral
dasatinib and oral lapatinib ditosylate once daily on days 1-28. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.

- Cohort II (treatment at the MTD): Patients receive oral dasatinib once daily on days 1
and 9-28, and oral lapatinib ditosylate once daily on days 2-28 of course 1. For all
subsequent courses, patients receive oral dasatinib and oral lapatinib ditosylate once
daily on days 1-28. Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.

Tissue and blood samples are collected periodically for pharmacokinetic and correlative
studies. Samples are analyzed for biomarkers, circulating tumor cells, tyrosine
phosphorylated or total MAP-K, EGFR, Her2, and FAK, among other potential markers of
activity and/or response by immunofluorescence. Circulating osteoclasts are also assessed by
flow cytometry.

After completion of treatment study, patients are followed for 3 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed advanced solid tumor

- Unresectable disease

- Must be refractory to or have refused all standard treatment for the disease

- Willing to provide the biologic specimens (cohort II only)

- No known standard therapy for disease that is not refractory to treatment that is
potentially curative or definitely capable of extending life expectancy

- No CNS metastases that are not stable for at least 4 weeks prior to registration
based on imaging, clinical assessment, and use of steroids

- No uncontrolled pleural or pericardial effusion of any grade

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- Life expectancy ≥ 12 weeks.

- Absolute neutrophil count ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Total bilirubin ≤ upper limit of normal (ULN)

- AST ≤ 3 times ULN (5 times ULN if liver involvement)

- Creatinine ≤ 1.5 times ULN

- Hemoglobin ≥ 9.0 g/dL

- Potassium and magnesium must be within normal limits

- LVEF > 50% by ECHO

- Able to swallow pills

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 4 weeks
after completion of study therapy

Exclusion criteria:

- Uncontrolled infection

- New York Heart Association classification III or IV

- Seizure disorder

- Uncontrolled angina, congestive heart failure, or myocardial infarction within the
past 6 months

- Diagnosed 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)

- Hypokalemia or hypomagnesemia that cannot be corrected

- Diagnosed congenital bleeding disorders (e.g., von Willebrand disease)

- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII
antibodies)

- Ongoing or recent (≤ 3 months prior to registration) significant gastrointestinal
bleeding

- Gastrointestinal conditions that may interfere with drug absorption such as
ulcerative colitis, Crohn disease, and short bowel syndrome

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C)
and recovered

- More than 4 weeks since prior immunotherapy, or biologic therapy (i.e., bevacizumab,
trastuzumab [Herceptin®], or cetuximab)

- More than 4 weeks since prior molecular target agents (i.e., erlotinib hydrochloride,
sunitinib malate, sorafenib tosylate, gefitinib, imatinib mesylate)

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy to > 25% of bone marrow

- No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary
therapy considered investigational

- No concurrent therapy with a CYP3A4 inhibitor or inducer

- No concurrent prophylactic colony-stimulating factors

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Safety Issue:

Yes

Principal Investigator

Charles Erlichman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000593527

NCT ID:

NCT00662636

Start Date:

August 2008

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

Name

Location

Mayo ClinicRochester, Minnesota  55905
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224