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A Phase II Study of Dasatinib (NSC 732517) in Previously-Treated Patients With Metastatic Colorectal Cancer

Phase 2
18 Years
Open (Enrolling)
Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

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Trial Information

A Phase II Study of Dasatinib (NSC 732517) in Previously-Treated Patients With Metastatic Colorectal Cancer


I. Determine the progression-free survival of patients with metastatic colorectal cancer who
have progressed on or following two prior chemotherapy regimens and are then treated with


I. Determine the objective response rates in patients treated with dasatinib. II. Determine
the overall survival of patients treated with dasatinib. III. Determine the toxicity in
patients treated with dasatinib.


I. Determine the incidence of somatic mutations in c-src, c-yes, fyn, lck, hck, lyn, yrk and
csk in archival primary and metastatic colorectal cancer tissues from these patients and to
correlate this with clinical outcome.

II. Determine the incidence of total c-src and phosphorylated c-src expression in archival
primary and metastatic colorectal cancer specimens from these patients, and to correlate
this with clinical outcome.

III. Evaluate the effect of dasatinib on serum VEGF levels.

OUTLINE: This is a multicenter study. Patients receive oral dasatinib twice daily on days
1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable

Blood is collected on days 1 (prior to the first dose of dasatinib) and 15 of course 1 for
measurement of VEGF pre-and post-dasatinib administration. Archived tumor tissue (tumor or
core biopsy; primary or metastatic lesion) is collected for identification of the incidence
of somatic mutations and polymorphisms by polymerase chain reaction and electrophoresis and
for measurement of total c-src and phosphorylated src expression by immunohistochemistry.

After completion of study treatment, patients are followed for at least 8 weeks.

Inclusion Criteria:

- Histologically or cytologically confirmed colorectal cancer

- Metastatic disease

- Not curable by surgical resection

- Archival tumor tissue available

- Measurable disease, defined as at least one unidimensionally measurable lesion ≥ 20
mm by conventional techniques or ≥ 10 mm by spiral CT scan

- Measurable disease must be outside of a prior radiation port

- Documented disease progression either during or after prior chemotherapy treatment

- No more than 2 prior chemotherapy regimens in the adjuvant or metastatic setting

- Prior chemotherapy regimens must have contained a fluoropyrimidine (e.g.,
fluorouracil or capecitabine), oxaliplatin, and irinotecan

- Patients who received no prior adjuvant therapy must have received 2 prior
chemotherapy regimens for metastatic disease (e.g., FOLFOX followed by

- Patients who received prior adjuvant therapy with a fluoropyrimidine plus
oxaliplatin must have received no more than 1 chemotherapy regimen for
metastatic disease that must have contained irinotecan

- VEGF or EGFR inhibitors with prior chemotherapy allowed

- No known brain metastases

- Life expectancy > 3 months

- ECOG performance status (PS) 0-2 or Karnofsky PS ≥ 60%

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 2.5 times ULN (5 times ULN with liver metastases)

- Creatinine normal or creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to dasatinib

- No QTc prolongation, defined as a QTc interval ≥ 480 msecs (Bazett correction)

- No condition (e.g., gastrointestinal tract disease resulting in an inability to take
oral medication or a requirement for IV alimentation, or active peptic ulcer disease)
that would impair ability to swallow and retain dasatinib tablets

- Prior partial colectomy is not considered an exclusion factor

- No clinically significant cardiovascular disease including any of the following:

- Myocardial infarction or ventricular tachyarrhythmia within the past 6 months

- New York Heart Association class II -IV congestive heart failure

- Major conduction abnormality (unless a cardiac pacemaker is present)

- No uncontrolled intercurrent illness including, but not limited to, any of the

- Ongoing or active infection

- History of significant bleeding disorder (including congenital [e.g., von
Willebrand's disease] or acquired [e.g., anti-factor VIII antibodies] disorders)

- Large pleural effusions

- Psychiatric illness or social situations that would limit compliance with study

- No currently active second malignancy other than non-melanoma skin cancer or
carcinoma in situ of the cervix

- Patients are not considered to have a currently active malignancy if they have
completed therapy and have no evidence of recurrence for at least 5 years

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
and recovered

- At least 4 weeks since prior radiation therapy and recovered

- No prior surgical procedures affecting absorption

- No prior treatment with inhibitors of src, PDGFR, KIT, or EPHA2

- More than 1 week since prior and no concurrent medications or substances that are
potent inhibitors or inducers of CYP3A4

- More than 1 week since prior and no concurrent medications that inhibit platelet
function (e.g., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel,
cilostazol, abciximab, ticlopidine, or any non-steroidal anti-inflammatory drug)

- More than 1 week since prior and no concurrent agents 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, or lidoflazine

- No concurrent anticoagulants (e.g., warfarin, heparin/low molecular weight heparin
[e.g., danaparoid, dalteparin, tinzaparin, or enoxaparin])

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent grapefruit or grapefruit juice

- No other concurrent investigational agents or commercial agents or therapies

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Description:

Progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Patients who are still alive and have not progressed will be censored as the data of the last negative examination. A Simon (1989), optimal, two-stage design will be employed.

Outcome Time Frame:

From the start of treatment to the time of disease progression or death from any cause, assessed at 4 months after completion of treatment

Safety Issue:


Principal Investigator

Hedy Kindler

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

Related Keywords:

  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms



University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470