AZD1775 continued access study to assess safety and tolerability for Patients Enrolled in AZD1775 Clinical Pharmacology Studies

Exclusion Criteria

• Patients must not enrol in this study if any of the following exclusion criteria are fulfilled:
• • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study centre).
• • Previous enrolment and received study treatment in the present study. Patients can, however, be re-screened if the reason for the screen failure no longer exists.
• • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
• • Must not have received another systemic anti-cancer therapy in the interval following participation in the AZD1775 clinical pharmacology study and the start of treatment on the CA protocol.
• • Not developed any clinical findings suggestive of brain metastasis. Patients continue to be neurological stable and remain off systemic corticosteroids following treatment of known brain metastases.
• • Did not tolerate AZD1775 in the parent study in the opinion of the Investigator.
• • Where a course of palliative radiotherapy was indicated, the last fraction must have been delivered before the start of study treatment on the CA study.
• • Major surgical procedures ≤28 days of beginning study treatment, or minor surgical
• procedures ≤7 days. No waiting period required following port-a-cath placement or other central venous access placement.
• • Grade >1 toxicities from prior therapy, according to the Common Terminology Criteria for Adverse Events (CTCAE), excluding alopecia or anorexia.
• • Continue to be able to swallow oral medication, did not undergo placement of a percutaneous endoscopic gastrostomy tube and did not require total parenteral nutrition.
• • Has had prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 between the
• parent study and entry into this CA study. Co administration of aprepitant or fosaprepitant during this study is prohibited.
• • Has consumed herbal preparations between the parent study and entry into this CA study.
• • Has consumed grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges between the parent study and entry into the CA study.
• • Any known hypersensitivity or contraindication to AZD1775 or to the components thereof.
• • Any of the following cardiac diseases currently or within the last 6 months as defined by the New York Heart Association ≥Class 2:
• - Unstable angina pectoris.
• - Congestive heart failure.
• - Acute myocardial infarction.
• - Conduction abnormality not controlled with pacemaker or medication.
• - Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac
• abnormalities are eligible).
• • AZD1775 should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial
• infarction.
• • Patient with mean resting QTc interval (specifically QTc calculated using the
• Fridericia formula [QTcF]) >450 ms for males and >470 ms for females from 3 electrocardiograms (ECGs) performed within 2 to 5 minutes apart during
• screening, or congenital long QT syndrome.
• • Pregnant or lactating female patients.
• • Serious, symptomatic active infection at the time of study entry, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment.
• • Active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).