Clinical trial NCT02610075 (phase 1, status: completed)
Conditions: locally advanced solid tumours, metastatic solid tumours, ovarian cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: azd1775
SMILES: CN1CCN(CC1)C1=CC=C(NC2=NC=C3C(=O)N(CC=C)N(C3=N2)C2=NC(=CC=C2)C(C)(C)O)C=C1
Eligibility criteria:

        Inclusion Criteria:

          1. Prior palliative radiation completed ≥ 7 days prior to the start of AZD1775 and
             recovered from any acute adverse effects.

          2. ECOG PS score 0 or 1.

          3. Baseline laboratory values:

               -  ANC ≥1500/μL

               -  Hemoglobin (HgB) ≥9 g/dL

               -  Platelets ≥100,000/μL

               -  ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.

               -  Serum bilirubin WNL or ≤1.5 x ULN in patients with liver metastases; or total
                  bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented
                  Gilbert's Syndrome.

               -  Serum creatinine ≤1.5 x ULN, or measured creatinine clearance ≥45 mL/min.

          4. Females who are not of child-bearing potential and fertile females of child-bearing
             potential who agree to use adequate contraceptive measures, who are not breastfeeding,
             and who have a negative serum or urine pregnancy test within 3 days prior to, and on
             the day of starting study treatment.

          5. Males willing to use at least one medically acceptable form of contraception for
             duration of study and for 3 months after treatment stops.

          6. Predicted life expectancy ≥12 wks.

          7. Age ≥18

          8. Histologically or cytologically documented locally advanced or metastatic solid
             tumour, excluding lymphoma, for which standard therapy does not exist or has proven
             ineffective or intolerable.

          9. Measurable or non-measurable disease according to RECIST v1.1.

        Exclusion Criteria:

          1. Use of a treatment drug 21 days or 5 half-lives (whichever is shorter) prior to
             AZD1775. For drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between
             termination of the prior treatment and administration of AZD1775 treatment is
             required.

          2. Use of an investigational drug during the past 30 days or 5 half-lives (whichever is
             longer) prior to first dose of study treatment.

          3. Major surgical procedures ≤28 days of beginning study treatment, or minor surgical
             procedures ≤7 days.

          4. Grade >1 toxicity from prior therapy (except alopecia or anorexia).

          5. Inability to swallow oral medications.

          6. Palliative radiation therapy completed ≤7 days prior to start of study drug.

          7. Known malignant CNS disease other than neurologically stable, treated brain
             metastases.

          8. Rx or non-Rx drugs or 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 which cannot be discontinued 2 weeks prior to dosing and
             withheld until 2 weeks after the last dose of study drug.

          9. Patients should stop using herbal medications 7 days prior to first dose of study
             treatment.

         10. Any of the following cardiac diseases currently or within the last 6 months as defined
             by New York Heart Association (NYHA) ≥ 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)

         11. History of Torsades de pointes unless all risk factors that contributed to Torsades
             have been corrected.

        11. Mean resting QTc interval >470 msec (as calculated per institutional standards) at
        study entry obtained from 3 ECGs within 5 minutes or congenital long QT syndrome.

        12. Pregnant or lactating. 13. Serious 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.

        14. Presence of other active invasive cancers. 15. Psychological, familial, sociological,
        or geographical conditions that do not permit compliance with protocol.