IGNITE: This phase II trial is testing an oral targeted therapy (adavosertib) in patients with high grade serous ovarian cancerA Phase II signal-seeking trial of Adavosertib (AZD1775) targeting recurrent high grade serous ovarian cancer (HGSC) with Cyclin E1 (CCNE1) over-expression with and without gene amplification to determine the clinical benefit rate

Exclusion

1. Patient has had prior treatment with Wee1 kinase inhibition
2. Use of anti-cancer treatment drug less than or equal to 21 days or 5 half-lives (whichever is shorter) prior to registration; for drugs for which 5 half-lives is less than or equal to 21 days, a minimum of 10 days between termination of the prior treatment and registration into the study is required
- Patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and may continue at the discretion of the investigator.
3. Patient has had previous radiation therapy completed less than or equal to 7 days prior to registration
4. Patient has had major surgical procedures less than or equal to 28 days prior to registration, or minor surgical procedures less than or equal to 7 days prior to registration:
- No waiting period required following port-a-cath or other central venous access placement
5. Patient has persistent Grade > 1 toxicity from prior therapy (except alopecia or anorexia)
6. Patient has an inability to swallow oral medications; Note: Patients may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN)
- Patients with symptoms subacute or acute bowel obstruction in three months prior to Cycle 1 Day 1 of main study are excluded
7. Patient has known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after treatment:
- Patients must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to registration
8. Patient has had prescription or non-prescription drugs or other products known to be moderate to strong inhibitors/inducers of CYP3A4. If the drug could be discontinued, then a wash out of greater than or equal to 2 weeks prior to Day 1 of dosing is required and the drug will be withheld throughout the study until 2 weeks after the last dose of study drug.
- Co-administration of aprepitant or fosaprepitant during this study is prohibited
- The use of sensitive CYP3A4 substrates could be used with caution. Clinical data showed that adavosertib is a weak inhibitor of CYP3A4.
9. Patient has taken the following herbal preparations within 7 days prior to registration:
- St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng.
10. Patient has known hypersensitivity or contraindication to the components of the study drug adavosertib
11. Patient has any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) greater than or equal to 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)
- Mean resting corrected QTc interval using the Fridericia formula (QTcF) > 470 msec (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
- History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected
12. Pregnant or breastfeeding women
13. Patient has serious active infection at the time of registration, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment
14. Patient has a presence of other active invasive cancers that do not harbor CCNE1 amplification
15. Patient has a known positive test result for human immunodeficiency virus (HIV) or active hepatitis B or C virus infection