Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer

NCT ID: NCT00504153

Last Updated: 2014-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2011-06-30

Brief Summary

This phase II trial is studying dasatinib to see how well it works in treating patients with previously treated metastatic colorectal cancer. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth.

Detailed Description

PRIMARY OBJECTIVES:

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 dasatinib.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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 toxicity.

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.

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (tyrosine Kinase Inhibitor)

Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

dasatinib

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BMS-354825; Sprycel

Eligibility Criteria

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 FOLFIRI)
• 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 following:

• 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 requirements
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hedy Kindler

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Chicago

Chicago, Illinois, United States

Countries

United States

Other Identifiers

NCI-2009-00223

Identifier Type: REGISTRY

Identifier Source: secondary_id

UCCRC-NCI-7786

Identifier Type: -

Identifier Source: secondary_id

CDR0000557036

Identifier Type: -

Identifier Source: secondary_id

15431A

Identifier Type: OTHER

Identifier Source: secondary_id

7786

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00223

Identifier Type: -

Identifier Source: org_study_id