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Study Summary
No. 2006-1097:.......Advanced Cancers......Razelle Kurzrock......Investigational Cancer Therapeutics
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Study Summary Title
Study Summary
Number:
2006-1097
Study Title:A Phase I, Open-Label, Multi-Center Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of AZD8330 in Patients with Advanced Malignancies
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Physician New Patient Referral
Name:Razelle KurzrockPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Investigational Cancer TherapeuticsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-563-1930
Contact us about clinical trials
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General Information
Disease Group:Advanced CancersSupported By:AstraZeneca
Phase of Study:Phase IReturn
Visit:
Patients enrolled in Part A will come to the clinic weekly for weeks 1 - 5.
Patienta will then return once every 4 weeks.
Treatment
Agents:
AZD8330Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of AZD8330 that can be given to patients with advanced cancer. The safety of
the drug, how it is absorbed in the blood, and its effect on the body will also
be studied.
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Study Objectives / Outcomes
Primary
The primary objective is to assess the safety and tolerability of AZD8330 in patients with advanced solid malignancies.

Secondary
The secondary objectives are as follows:
  • To determine the pharmacokinetics (PK) of AZD8330 and any known major metabolites following both single and multiple oral dosing of AZD8330 in patients with advanced solid malignancies.
  • To investigate possible relationships between plasma AZD8330 and/or metabolite concentrations/exposure and changes in safety and pharmacodynamic (PD) parameters.
  • To investigate the effect of AZD8330 treatment on pERK in PBMCs in patients with advanced malignancies.

Exploratory
The exploratory objectives are as follows:
  • To obtain a preliminary assessment of efficacy of AZD8330.
  • To collect a blood sample (optional) for DNA extraction and storage to investigate whether variability in the AZD8330 PK, safety, efficacy or PD results could be explained by differences in the patient's genotype.
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Study Status Information
Study Activation / Registration Date:03/20/2007
IRB Review and Approval Date:03/20/2007
Study Type:Phase I
Recruitment Status:Terminated
Projected Accrual:85
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Provision of informed consent.

2) Male or female, aged 18 years or older.

3) Cancer which is refractory to standard therapies, or for which no standard therapies exist. For part B patients will need to have tumor amenable to repeat biopsies.

4) Measurable Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/= 20mm with conventional techniques or as >/= 10mm with spiral CT scan or non-measurable lesions according to the RECIST Criteria.

5) Laboratory value (SI Units): Calculated serum creatinine clearance >/= 50 mL/min (using Cockcroft-Gault formula or by 24-hour urine collection)

6) LVEF as determined at baseline MUGA/echocardiography at or above the normal level.

7) WHO performance status 0-2 (those with performance status 2 must have been stable with no deterioration over the previous 2 weeks).

8) Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal patients. Post menopausal females are defined as follows: Natural menopause with menses >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses; serum FSH and LH and plasma oestradiol levels in the postmenopausal range for the institution; bilateral oophorectomy or hysterectomy.

9) FOR OPTIONAL GENETIC RESEARCH: Provision of informed consent for host genetic sampling (blood samples) and analyses.

Exclusion Criteria:1) Laboratory values (SI Units): Absolute Neutrophil Count (ANC) <1.5 x 10^9/L (1500 per mm^3); Platelets <100 x 10^9/L (100,000 per mm^3); Hemoglobin (Hgb) <9.0 g/dL; serum bilirubin >/= 1.5x Upper Limit of Normal (ULN); aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT)>/= 2.5 x ULN; and serum calcium >1 x ULN and phosphate >1 x ULN; serum calcium (corrected for albumin^2) outside of normal limits; phosphate outside of normal limits; and serum potassium or magnesium outside of normal limits.

2) Any radiotherapy, biological or chemotherapy within 21 days prior to starting the study (not including palliative radiotherapy at focal sites) or who have not recovered from side effects of their treatment

3) Participation in an investigational drug study within the 30 days prior to entry or who have not recovered from clinically significant side effects of an investigational study drug

4) Brain metastases or spinal cord compression unless treated and stable off steroids and anticonvulsants (for at least 1 month)

5) Female patients who are breast feeding, or patients of reproductive potential not employing an effective method of birth control

6) Any evidence of severe or uncontrolled systemic disease (e.g., severe hepatic impairment, severe renal impairment uncontrolled diabetes, acute uncontrolled infection) or current unstable or uncompensated respiratory or cardiac conditions or peripheral vascular disease including diabetic vasculopathy

7) Parathyroid disorder or history of malignancy associated hypercalcemia

8) Evidence of active infection or active bleeding diatheses

9) Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment

10) Patients with documented cases of human immunodeficiency virus (HIV) or hepatitis B or C

11) Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

12) Previous treatment with a MEK inhibitor

13) Mean QT interval > 450ms

14) Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)

15) Previous enrollment or randomization of treatment in the present study

16) Clinical judgement by the Investigator that the patient should not participate in the study

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Links
Registration Number: NCT00454090
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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