Dasatinib and Lapatinib Ditolsylate in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00662636
Recruitment Status : Completed
First Posted : April 21, 2008
Last Update Posted : March 23, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:

RATIONALE: Dasatinib and lapatinib ditoslylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib and lapatinib ditoslylate when given together in treating patients with advanced solid tumors that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: dasatinib Drug: lapatinib ditosylate Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Detailed Description:


I. To determine the maximally tolerated dose of dasatinib combined with lapatinib.

II. To describe the toxicities associated with this treatment combination. III. To assess the pharmacokinetic interaction of lapatinib and dasatinib. IV. To assess the effect of the lapatinib and dasatinib combination on circulating tumor cells and on osteoclast precursor activation.

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

VI. To describe the responses of this treatment combination.

OUTLINE: This is a multicenter, phase I, dose-escalation study. COHORT I: Patients receive oral dasatinib and oral lapatinib ditosylate once daily on days 1-28.

COHORT II: 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. In all subsequent courses patients receive oral dasatinib and oral lapatinib ditosylate once daily on days 1-28.

In both cohorts courses repeat every 28 days, in the absence of disease progression or unacceptable toxicity.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of the Combination of Dasatinib and Lapatinib
Actual Study Start Date : August 2008
Actual Primary Completion Date : December 18, 2014
Actual Study Completion Date : December 18, 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm I
Patients receive oral dasatinib and lapatinib ditosylate once daily on days 1-28.
Drug: dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel

Drug: lapatinib ditosylate
Given orally
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb

Other: pharmacological study
Correlative study (cohort II only)
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative study (cohort II only)

Primary Outcome Measures :
  1. Adverse events profile
  2. Toxicity profile per NCI CTCAE v3.0
  3. Response profile [ Time Frame: Every 4 weeks ]
  4. Time until any treatment-related toxicity, time until treatment-related grade 3+ toxicity, and time until hematologic nadirs (WBC, ANC, platelets)
  5. Time to progression and time to treatment failure
  6. Laboratory correlates

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologic proof of cancer that is now unresectable and refractory to or refused all standard treatment for the disease
  • Please contact study investigator and/or consult protocol document for specific details on laboratory criteria
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic for follow up
  • Life expectancy >= 12 weeks
  • Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
  • Echocardiogram with ejection fraction > 50%
  • ECOG performance status (PS) 0-2
  • Able to swallow pills whole (patients with feeding tubes may be eligible if whole pills can be taken and tolerated through the feeding tube)
  • Willingness to provide the biologic specimens as required by the protocol for Cohort II, (MTD) patients only

Exclusion Criteria:

  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • Pregnant women
  • Any of the following prior therapies: chemotherapy =< 4 weeks prior to registration; mitomycin C/nitrosoureas =< 6 weeks prior to registration; immunotherapy =< 4 weeks prior to registration; biologic therapy =< 4 weeks prior to registration
  • Patients who have been treated with Avastin, Herceptin, or Erbitux are eligible if last treatment is >= 4 weeks; molecularly targeted agents (erlotinib, sunitinib, sorafenib, gefitinib, imatinib) =< 4 weeks prior to registration; radiation therapy =< 4 weeks prior to registration; radiation to > 25% of bone marrow
  • CNS metastases that are not stable for at least 4 weeks prior to registration based on imaging, clinical assessment, and use of steroids
  • Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and until 4 weeks following study
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
  • Current therapy with a CYP3A4 inhibitor or inducer
  • Known standard therapy for the patient's disease that is not refractory to treatment that is potentially curative or definitely capable of extending life expectancy
  • Uncontrolled pleural or pericardial effusion of any grade
  • Uncontrolled angina, congestive heart failure or MI within 6 months prior to registration
  • Diagnosed congenital long QT syndrome
  • Any 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)
  • Subjects with potassium or magnesium that are not within normal limits and cannot be corrected prior to registration
  • New York Heart Association classification III or IV
  • 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
  • Prophylactic use of colony-stimulating factors during the study is not allowed
  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • G.I conditions that may interfere with drug absorption such as Ulcerative Colitis, Crohn's Disease, and Short Bowel Syndrome
  • Active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator's assessment)
  • Nursing women
  • Uncontrolled infection
  • Seizure disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00662636

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Charles Erlichman Mayo Clinic

Responsible Party: Mayo Clinic Identifier: NCT00662636     History of Changes
Other Study ID Numbers: MC0616
NCI-2009-01197 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC0616 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: April 21, 2008    Key Record Dates
Last Update Posted: March 23, 2017
Last Verified: April 2016

Additional relevant MeSH terms:
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action