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Phase II Study of AZD0530 (NSC 735464) in Patients With Previously Treated Metastatic Colorectal Cancer

Phase 2
18 Years
Not Enrolling
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

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Trial Information

Phase II Study of AZD0530 (NSC 735464) in Patients With Previously Treated Metastatic Colorectal Cancer


I. Determine the progression-free survival (PFS) at 4 months in metastatic colorectal
carcinoma patients receiving daily doses of AZD0530.


I. Evaluate the objective response rate (RR) and overall survival (OS) of patients with
metastatic colorectal cancer who are treated with AZD0530.

II. In patients who consent, both blood and tissue samples will be collected for laboratory
correlates. Assess in a preliminary manner the association between correlative markers and
the potential downstream effects of AZD0530 on IL-8, VEGF, specific Src-regulated markers in
focal adhesions, adherens junctions, and angiogenesis on clinical outcome in pre- and
post-treatment tumor samples.


Patients receive oral AZD0530 once daily on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3
months thereafter.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

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)

Type of Study:


Study Design:

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

Outcome Measure:

Proportion of metastatic colorectal patients with 1 previous treatment who are alive and progression free after commencing the experimental therapy

Outcome Description:

95% posterior credible intervals will be used.

Outcome Time Frame:

Time from start of treatment to time of progression, up to 4 months

Safety Issue:


Principal Investigator

Cathy Eng

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2006

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Rectal Neoplasms



M D Anderson Cancer Center Houston, Texas  77030