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Study Summary
No. 2007-0671:.......Brain; CNS......John DeGroot......Neuro Oncology
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Study Summary Title
Study Summary
Number:
2007-0671
Study Title:A Phase III, Randomised, Parallel Group, Multi-Centre Study in
Recurrent Glioblastoma Patients to Compare the Efficacy of Cediranib
[RECENTIN™, AZD2171] Monotherapy and the Combination of
Cediranib with Lomustine to the Efficacy of Lomustine Alone
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Physician New Patient Referral
Name:John DeGrootPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Neuro OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2883
Contact us about clinical trials
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General Information
Disease Group:Brain
CNS
Supported By:AstraZeneca AB
Phase of Study:Phase IIIReturn
Visit:
every 3 for first cycle, then every 6 weeks
Treatment
Agents:
AZD2171
Lomustine
Home Care:Patients will take the investigational drug at home
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 compare lomustine given with
cediranib, cediranib alone, and lomustine alone in the treatment of
glioblastoma. The safety of cediranib when given with and without lomustine
will also be studied.
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Study Objectives / Outcomes
Primary Objective

The primary objective of the study is to determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine ) compared to oral lomustine alone by assessment of progression free survival (PFS) as assessed by independent radiographic radiological review.

Secondary Objectives
  • To determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone by assessment of Overall Survival (OS)
  • To determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone by assessment of radiographic Response Rate (RR).
  • To determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine ) compared to oral lomustine alone by assessment of alive and progression free rate at 6 months defined as 24 weeks (APF6), after randomization
  • To determine the steroid sparing effects of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone by assessment of average daily steroid dosage change from baseline until progression and average number of progression/steroid free days.
  • To determine the time to deterioration of the neurological status of subjects receiving cediranib (either in monotherapy or in combination with oral lomustine ) compared to oral lomustine alone.
  • To determine in subjects with neurological symptoms at baseline, an improvement in neurological symptoms (visual disorder, motor dysfunction, communication deficit, and drowsiness) concurrent with stable or decreasing steroid use for subjects receiving cediranib monotherapy or in combination with oral lomustine compared to subjects receiving oral lomustine alone as measured by the EORTC brain tumor module BN-20 by patient reported outcome
  • To determine the safety and tolerability of cediranib (either in monotherapy and in combination with oral lomustine).

Exploratory Objectives
  • To investigate the impact of cediranib treatment on social functioning, role functioning, health related quality of life, and other domains of the European Organization for Research and Treatment of Cancer – Quality of Life Questionnaire (EORTC QLQ)-C30 and BN-20.
  • Based on the Karnofsky PS, investigate the TDPS (time to deterioration in patient Karnofsky Performance Status [PS]) during the period of treatment with investigational therapy (pre and post progression).
  • To investigate subject health status during the period of the study based on the EuroQoL 5 Dimension Instrument (EQ-5D)
  • To investigate the relationship between the effects of cediranib on soluble angiogenesis biomarkers and clinical efficacy.
  • To obtain optional blood samples for pharmacogenetics.
  • To obtain optional archival tumor biopsy samples for biomarker analysis
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Study Status Information
Study Activation / Registration Date:01/08/2009
IRB Review and Approval Date:03/21/2008
Study Type:Phase Iii
Recruitment Status:Closed
Projected Accrual:300
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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) Age >/=18 years

2) Life expectancy (an average length of survival of patients in a similar situation) >/= 12 weeks

3) Histological/cytological confirmation of glioblastoma

4) Patients with measurable disease (contrast-enhancing tumour >/=10 mm by shortest diameter on 2 axial slices) by MRI imaging within 4 weeks prior to enrolment (Visit 1). Or patients who have undergone a resection without measurable disease prior to enrolment.

5) Patients must have been on no steroids or a stable dose of steroids for at least 5 days before the baseline MRI (Visit 2)

6) Patients must have failed standard frontline treatment for glioblastoma including surgery (with exception, if patient does not receive surgery as part of frontline treatment due to anatomical location, based on neurosurgeon's assessment), cranial radiotherapy and chemotherapy with temozolomide. The last dose of temozolomide must be more than 28 days from randomization. GliadelŪ wafers are permitted, as it is part of local treatment.

7) Patients must have a Karnofsky Performance Score of 70 or above

8) Patients must have a mini-mental status examination score of 15 or greater

9) Provision of informed consent

10) Patients who require either oral anticoagulants (coumadin, warfarin) or low molecular weight heparin are eligible provided there is increased vigilance with respect to monitoring INR

Exclusion Criteria:1) Patients on enzyme-inducing anti-epileptic drugs within 2 weeks prior to randomisation. - Note: Patients are eligible if they switched to non-enzyme inducing agents and discontinued enzyme-inducing agents for more than or equal to 2 weeks prior to randomisation.

2) Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count </=1.5 x 10^9 /L or platelet count </=100 x 10^9 /L or requiring regular blood transfusions to maintain haemoglobin >9g/dL

3) Serum bilirubin >/=1.5 x ULRR(except for patients with known documented cases of Gilbert's Syndrome)

4) ALT or AST >/= 2.5 x ULRR

5) Serum creatinine > 1.5 x ULRR or a creatinine clearance of </= 50mL/min calculated by Cockcroft-Gault

6) Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein < 1.5g in a 24 hr period or UPC ratio <1.5

7) History of significant gastrointestinal impairment including malabsorption disorders due to structural defects such as post-gastrectomy, radiation enteritis, congenital or acquired reduction in absorptive surface, etc., as judged by the Investigator, that would significantly affect the absorption of AZD2171, including the ability to swallow the tablet whole

8) Patient with a history of poorly controlled hypertension with resting blood pressure > 150/100mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy, or patients who are requiring maximal doses of calcium channel blockers to stabilise blood pressure

9) Any evidence of severe or uncontrolled diseases (eg, unstable or uncompensated respiratory, cardiac, hepatic or renal disease)

10) Unresolved toxicity > CTCAE grade 1 from previous anti-cancer therapy (including radiotherapy) except alopecia (if applicable)

11) Mean QTc with Bazetts correction >470msec in screening ECG or history of familial, long QT syndrome

12) Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks)

13) Recent (<14 days) major thoracic or abdominal surgery or brain biopsy. Recent craniotomy(<28 days) prior to first dose, or a surgical incision that is not fully healed

14) Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication

15) Known hypersensitivity to cediranib or any of its excipients

16) History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the subject has been disease free for 2 years and they have tissue diagnosis of the target lesion.

17) Known active infection with hepatitis B or C or HIV

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

19) Previous enrolment or randomisation of treatment in the present study.

20) Treatment with an investigational drug within 30 days prior to the first dose of cediranib

21) Other concomitant anti-cancer therapy except steroids

22) Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy

23) Patients with evidence of any intratumoral or peritumoral haemorrhage deemed significant by the treating physician

24) Patients who have received any form of cranial radiation within 3 months prior to study entry.

25) Known hypersensitivity to lomustine or any of its excipients

26) Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO). However, patients with values less than these for either FVC or DLCO may still be eligible for enrolment provided that lung pathology has been excluded after a full consultation by a pulmonologist including additional tests, for example: a high resolution CT scan

27) Patients who have progressed within 3 months of completion of standard cranial radiation

28) Patients that have received radiosurgery or brachytherapy

29) Patients with Celiac Disease

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Links
Registration Number: NCT00777153
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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