Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00504153
First received: July 17, 2007
Last updated: November 15, 2013
Last verified: November 2013

July 17, 2007
November 15, 2013
May 2007
June 2011   (final data collection date for primary outcome measure)
Progression-free Survival Rate [ 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 (i.e., up to 12 months.) ] [ Designated as safety issue: No ]
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 at the date of the last negative examination. A Simon (1989), optimal, two-stage design will be employed. The progression-free survival count will be the proportion of subjects who are alive and progression-free at 4 months.
Progression-free survival at 4 months
Complete list of historical versions of study NCT00504153 on ClinicalTrials.gov Archive Site
  • Response Rate (RR) (Complete or Partial Responders) [ Time Frame: Every 2 courses, assessed up to 8 weeks after completion of study treatment (i.e., up to 10 months) ] [ Designated as safety issue: No ]
    Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. The response rate is the proportion of subjects who experienced a complete or partial response.
  • Incidence of Somatic Mutations [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Multivariable analysis of progression-free survival duration will be performed using the Cox (1972) regression model to evaluate the prognostic value of somatic mutations. For the mutational analysis endpoints, genetic mutations will also be correlated with drug activity via Fisher's exact test for comparisons of responders with non-responders and for comparison of patients progression-free and 4 months vs. those with early progression or death
  • Association Between the Incidence of Total C-src and Phosphorylated C-src Expression and Response [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Examined by comparing expression in those who have an objective response versus those who do not and in those with and without disease progression at 4 months using Fisher's exact test.
  • Change in Plasma Vascular Endothelial Growth Factor (VEGF) Levels Over 15 Days [ Time Frame: At baseline and day 15 ] [ Designated as safety issue: No ]
    Changes of VEGF will be correlated with response rates and 4-month progression-free survival utilizing the Wilcoxon rank-sum test.
  • Clinical efficacy including response rates (complete and partial responders) and overall survival
  • Safety
  • Toxicity according to the CTC 3.0 criteria
  • Frequency of adverse events summarized by type and grade
Not Provided
Not Provided
 
Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer
A Phase II Study of Dasatinib (NSC 732517) in Previously-Treated Patients With Metastatic Colorectal Cancer

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

We conducted a multi-center phase II trial of dasatinib in unresectable, previously-treated metastatic colorectal cancer (CRC) patients. The primary endpoint of this study was the progression-free survival (PFS) rate at 4 months. Secondary endpoints included objective response rate (complete response + partial response), toxicity, and overall survival. PFS and overall survival were calculated from the start of study treatment. The trial was conducted using a Simon optimal 2-stage design to test the null hypothesis that the 4-month PFS rate was less than or equal to 20% versus the alternative that it was at least 40%. Nineteen patients were to be enrolled in the first stage, and all patients were to be evaluable for the primary endpoint. Those with early discontinuation of treatment or early death were considered treatment failures. If four or fewer patients were alive and progression-free at 4 months, the trial would be terminated for lack of efficacy. Otherwise, an additional 35 patients would be accrued, and if 16 or more patients (out of the 54) were alive and progression-free at 4 months, the drug would be considered worthy of further study. This design yields a 0.90 probability of a positive result if the true 4-month PFS rate is at least 40%. Progression-free and overall survival curves were constructed using the method of Kaplan and Meier. Confidence intervals for the median PFS and overall survival times were derived as described by Brookmeyer and Crowley.

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 vascular endothelial growth factor (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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
Drug: dasatinib
Other Names:
  • BMS-354825
  • Sprycel
Experimental: Dasatinib (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.
Intervention: Drug: dasatinib
Sharma MR, Wroblewski K, Polite BN, Knost JA, Wallace JA, Modi S, Sleckman BG, Taber D, Vokes EE, Stadler WM, Kindler HL. Dasatinib in previously treated metastatic colorectal cancer: a phase II trial of the University of Chicago Phase II Consortium. Invest New Drugs. 2012 Jun;30(3):1211-5. doi: 10.1007/s10637-011-9681-x. Epub 2011 May 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
19
Not Provided
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically/cytologically confirmed colorectal cancer

    • Metastatic disease
    • Not curable by surgery
    • Archival tumor tissue available
  • Measurable disease, defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

    • Measurable disease must be outside of prior radiation port
  • Documented disease progression during or after prior chemotherapy
  • No more than 2 prior chemotherapy regimens (adjuvant or metastatic)

    • Prior chemotherapy regimens must have contained a fluoropyrimidine, oxaliplatin, and irinotecan

      • Patients who received no prior adjuvant therapy must have received 2 prior chemotherapy regimens for metastatic disease
      • 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
      • Vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR) inhibitors with prior chemotherapy allowed
  • No known brain metastases
  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS ≥ 60%
  • white blood cell (WBC) ≥ 3,000/mm³
  • absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelets ≥ 100,000/mm³
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 times ULN (5 x 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 (QTc interval ≥ 480 milliseconds, Bazett correction)
  • No condition that would impair ability to swallow and retain dasatinib tablets

    • Prior partial colectomy is not an exclusion factor
  • No clinically significant cardiovascular disease including:

    • 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
    • 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
  • > 1 week since prior and no concurrent medications or substances that are potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4)
  • > 1 week since prior and no concurrent medications that inhibit platelet function
  • > 1 week since prior and no concurrent agents that are generally accepted to have a risk of causing Torsades de Pointes
  • No concurrent anticoagulants
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00504153
NCI-2009-00223, N01CM62201, CDR0000557036, 15431A
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Hedy Kindler University of Chicago Comprehensive Cancer Center
National Cancer Institute (NCI)
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP