AZD0530 (NSC 735464) in Treating Patients With Previously Treated Metastatic Colon Cancer or Rectal Cancer
Condition: Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: saracatinib; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Saracatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well AZD0530 works in treating patients with previously
      treated metastatic colon cancer or rectal cancer. AZD0530 may stop the growth of tumor cells
      by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed adenocarcinoma of the
             colon or rectum that is metastatic

          -  Patients must have measurable disease, defined (per RECIST criteria) as at least one
             lesion that can be accurately measured in at least one dimension (longest diameter to
             be recorded) as >= 20 mm with conventional techniques or >= 10 mm with spiral CT scan

          -  Patients must have received one and only one prior chemotherapy regimen for metastatic
             colorectal cancer; patients may have received biologic therapy (e.g., bevacizumab) in
             combination with chemotherapy as part of their prior chemotherapy

          -  ECOG performance status 0-2

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin =< 1.5 x institutional ULN

          -  AST(SGOT)/ALT(SGPT) =< 3.0 x institutional ULN

          -  Creatinine within normal institutional limits OR estimated CrCl (Cockcroft-Gault) or
             24 hr urine collection of >= 50 mL/min

          -  The effects of AZD0530 on the developing human fetus at the recommended therapeutic
             dose are unknown; however, AZD0530 has been shown to cause gross fetal malformations
             and to negatively impact embryo fetal survival in rats; for this reason and because
             many tyrosine kinase inhibitors are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) prior to study entry, for the duration of study
             participation, and up to 30 days following removal from the study; should a woman
             become pregnant or suspect she is pregnant while participating in this study, she
             should inform her treating physician immediately; women of child-bearing potential
             will have serum beta-Hcg levels drawn up to 7 days prior to receiving study treatment

          -  Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with AZD0530, breastfeeding should be
             discontinued if the mother is treated with AZD0530

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to study registration or those who have not
             recovered from treatment related adverse events > grade 1 (except for neuropathy [ies]
             which may be =< grade 2) due to agents administered more than 4 weeks earlier

          -  Use of specifically prohibited CYP3A4-active agents or substances are not permitted
             during protocol treatment, and patients who must continue treatment with these agents
             are not eligible; prohibited drugs should be discontinued seven (7) days or 5
             half-lives (whichever is the longer time period) prior to the administration of the
             first dose of AZD0530 and for 7 days or 5 half-lives (which ever is the longer time
             period) following discontinuation of AZD0530

          -  Patients may not be receiving any other investigational agents

          -  Patients with greater than +1 proteinuria on two consecutive readings taken no less
             than 24 hours apart are ineligible

          -  Patients with QTc prolongation (defined as a QTc interval greater than or equal to 480
             msecs) are ineligible

          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
             or active infection (requiring parenteral antibiotics at the time of registration),
             cardiac disease NYHA class III or IV, unstable angina pectoris, unstable cardiac
             arrhythmia or tachycardia (heart rate >= 100 beats per minute), poorly controlled
             hypertension (systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90
             mmHg)

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for IV alimentation, prior surgical
             procedures affecting absorption, or active peptic ulcer disease) that impairs their
             ability to swallow AZD0530 tablets are excluded

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  Pregnant women are excluded from this study because AZD0530 has the potential for
             teratogenic or abortifacient effects as shown by the gross fetal malformation and
             effects on embryofetal survival seen in reproductive toxicity studies in the rat

          -  Patients with a history of another primary malignancy within the last 5 years, with
             the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix

          -  Patient who are known to be HIV-positive are ineligible because of the potential for
             pharmacokinetic interactions with AZD0530 and antiretroviral therapy (HAART)