AZD7451 for Recurrent Gliomas

• Register: ClinicalTrials.gov
• Last refreshed on: 25 February 2013
• Main ID: NCT01468324
• Date of registration: 05/11/2011
• Primary sponsor: National Cancer Institute (NCI)
• Public title: AZD7451 for Recurrent Gliomas
• Scientific title: Phase I Trial of AZD7451, A Topomysin-Receptor Kinase (TRK) Inhibitor, For Adults With Recurrent Gliomas
• Date of first enrolment: October 2011
• Target sample size: 60
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01468324
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

• Name: Amanda W Wiggins

• Name: Katharine A McNeill, M.D.
• Affiliation: National Cancer Institute (NCI)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

- Patients with histologically proven malignant primary gliomas who have progressive
disease after radiotherapy will be eligible for this protocol.

- Patients must have an MRI scan performed within 14 days prior to registration and on
a fixed dose of steroids for at least 5 days. If the steroid dose is increased
between the date of imaging and registration a new baseline MRI is required.

- Patients having undergone recent resection of recurrent or progressive tumor will be
eligible as long as all of the following conditions apply:

1. Patients will be eligible four weeks after surgery if they have recovered from
the effects of surgery.

2. Residual disease following resection of recurrent tumor is not mandated for
eligibility into the study. To best assess the extent of residual disease
postoperatively, an MRI should be done:

- no later than 96 hours in the immediate post-operative period or

- at least 4 weeks post-operatively, and

- within 14 days of registration, and

- on a stable steroid dosage for at least 5 days.

If the 96 hour scan is more than 14 days before registration, the scan needs to be
repeated. If the steroid dose is increased between the date of imaging and registration, a
new baseline MRI is required on a stable steroid dosage for at least 5 days.

- Patients must have failed prior radiation therapy.

- Ability of subject or Legally Authorized Representative (LAR) (if the patient is
deemed by the treating physician to be cognitively impaired or questionably impaired
in such a way that the ability of the patient to give informed consent is
questionable) to understand and the willingness to sign a written informed consent
document indicating that they are aware of the investigational nature of this study.

- Patients must be greater than or equal to18 years old, and must have a life
expectancy > 8 weeks. Because no dosing or adverse event data are currently
available on the use of AZD7451 in patients < 18 years of age, children are excluded
from this study, but may be eligible for future pediatric trials.

- Patients must have a Karnofsky performance status of greater than or equal to 60

- Patients must be at least 4 weeks from radiation therapy. Additionally, patients must
be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from
procarbazine, 2 weeks from vincristine and 2 weeks from last bevacizumab
administration. Patients must be at least 4 weeks from other cytotoxic therapies not
listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen)
including investigative agents. With the exception of alopecia, all toxicities from
prior therapies should be resolved to CTCAE less than or equal to grade 1.

- Patients must have adequate bone marrow function (WBC greater than or equal to
3,000/microl, ANC greater than or equal to 1,500/mm(3), platelet count of greater
than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 9 gm/dl),
adequate liver function (AST, ALT and alkaline phosphatase less than or equal to 2.5
times ULN and bilirubin less than or equal to 1.5 times ULN), and adequate renal
function (creatinine less than or equal to 1.5 times ULN and/or creatinine clearance
greater than or equal to 50 cc/min calculated by Cockcroft-Gault) before starting
therapy. Patients must also have serum potassium greater than or equal to 3.5 mmol/L,
magnesium, phosphate and calcium levels within normal levels; supplementation is
allowed. In cases where the serum calcium is below the normal range, 2 options would
be available: 1) the calcium adjusted for albumin is to be obtained and substituted
for the measured serum value. Exclusion is to then be based on the adjusted for
albumin values falling below the normal limit. 2) Determine the ionized calcium
levels. Exclusion is then to be based on whether these ionized calcium levels are out
of normal range despite supplementation. These tests must be performed within 14 days
prior to registration. Eligibility level for hemoglobin may be reached by
transfusion.

- Patients must either not be receiving steroids, or be on a stable dose of steroids
for at least five days prior to registration.

- The effects of AZD7451 on the developing human fetus are unknown. For this reason and
because AZD7451 is 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 and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while she or
herpartner is participating in this study, the treating physician should be informed
immediately.

- A 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial entry with
QTc less than or equal to 470 msec.

- Patients must have normal left ventricular ejection fraction (LVEF greater than or
equal to 55% or normal by NIH Clinical Center criteria).

EXCLUSION CRITERIA:

- Patients who, in the view of the treating physician, have significant active hepatic,
renal, pulmonary or psychiatric diseases are ineligible.

- 2 Prior treatment with AZD7451.

- History of hypersensitivity to active metabolites or excipients of AZD7451.

- Clinically significant cardiovascular event (e.g. myocardial infarction, angina
pectoris, coronary artery bypass graft, angioplasty, vascular stent, superior vena
cava syndrome (SVC), New York Heart Association (NYHA, Appendix I) classification of
heart disease > 2 within 6 months before entry; or presence of cardiac disease that,
in the opinion of the investigator, increases the risk of ventricular arrhythmia.

- Hemorrhagic or ischemic stroke, including transient ischemic attacks and other
central nervous system bleeding in the preceding 6 months that were not related to
glioma surgery. History of prior intratumoral bleeding is not an exclusion criterion;
patients with history of prior intratumoral bleeding, however, need to undergo a
non-contrast head CT to exclude acute blood.

- Ventricular arrhythmias requiring continuous therapy or asymptomatic sustained
ventricular tachycardia within 12 months before study entry. Continuous or
intermittent atrial fibrillation requiring treatment. Patients with significant ECG
abnormalities such as complete left bundle block and third degree heart block are not
eligible.

- QTc prolongation with other medications that required discontinuation of that
medication.

- Congenital long QT syndro


Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Anaplastic Astrocyloma

Glioblastoma Multiforme

Gliosarcoma

Malignant Glioma

Oligoastrocytoma

Intervention(s)

Drug: AZD7451

Primary Outcome(s)

To establish the maximum tolerated dose of AZD7451 on a continuous once daily schedule in patients with recurrent gliomas not on enzyme-inducing anti-epileptic drugs (EIAED). [Time Frame: 3 years]

Secondary Outcome(s)

To obain exploratory information about the anti-tumor activity of AZD7451. [Time Frame: 3 years]

Secondary ID(s)

12-C-0005

120005

Source(s) of Monetary Support

Please refer to primary and secondary sponsors