AZD1775 in Treating Patients with Advanced Refractory Solid Tumors with CCNE1 Amplification

Inclusion Criteria

• Patients must have one of the histologically advanced solid tumors harboring CCNE1 amplification: Their diseases are refractory to, or do not have, standard-of-care therapy; or they declined standard-of-care therapy; CCNE1 amplification is defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory: CCNE1 amplification > 7 based on targeted custom Ampliseq panel on the Ion Torrent Personal Genoma Machine (PGM); or CCNE1 amplification on alternate CLIA platforms such as Foundation One, University of Washington (UW)-OncoPlex-Cancer Gene Panel, Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT), Solid Tumor Genomic Assay (Life Technologies), etc. will also be eligible to be treated after principal investigator (PI) approval; patients with known CCNE1 amplification on local or commercial platforms can start treatment after planned biopsy or submission of recent archival sample; central next generation sequencing (NGS) CCNE1 and fluorescence in-situ hybridization (FISH) testing will be performed to confirm the result
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Has read and understands the informed consent form (ICF) and has given written ICF prior to any study procedures; patients with impaired decision making capacity (IDMC) must have a close caregiver or legally authorized representative (LAR)
• Any prior radiation must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
• Absolute neutrophil count (ANC) >= 1500/uL (within 14 days of study drug[s] initiation)
• Hemoglobin (HgB) >= 9 g/dL for mono-therapy (within 14 days of study drug[s] initiation)
• Platelets >= 100,000/uL (within 14 days of study drug[s] initiation)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) or =< 5 x ULN if known hepatic metastases (within 14 days of study drug[s] initiation)
• Serum bilirubin < ULN or < 1.5 x ULN in patients with liver metastases; or total bilirubin < 3.0 x ULN with direct bilirubin within normal limits (WNL) in patients with well documented Gilbert’s syndrome (within 14 days of study drug[s] initiation)
• Serum creatinine =< 1.5 x ULN, or calculated creatinine clearance (CrCl) >= 45 mL/min as calculated by the Cockcroft-Gault method or 24-hour measured urine CrCl >= 45 mL/min (within 14 days of study drug[s] initiation)
• Female patients who are not of child-bearing potential and fertile females of childbearing potential who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to the start of study treatment; male patients willing to abstain or use barrier contraception (i.e. condoms) for the duration of the study and for 3 months after treatment stops
• Willingness and ability to comply with study and follow-up procedures
• Ability to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or other conditions that may hamper compliance and/or absorption of the study agent
• No prior treatment with wee1 kinase inhibition
• Provision of an archival tissue block, or 10 formalin-fixed paraffin-embedded (FFPE) slides, if available, and if not available having biopsiable disease and agreeing to pre-treatment biopsies

Exclusion Criteria

• Use of anti-cancer treatment drug =< 21 days or 5 half-lives (whichever is shorter) prior to the first dose of 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
• Previous radiation therapy completed =< 7 days prior to the start of study drugs
• Major surgical procedures =< 28 days of beginning AZD1775, or minor surgical procedures =< 7 days; no waiting period required following port-a-cath or other central venous access placement
• Unresolved grade 2 toxicity from prior therapy (except alopecia or anorexia)
• Patient has an inability to swallow oral medications; Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN)
• No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy [except for palliative local radiotherapy]), biological therapy or other novel agent is to be permitted while the patient is receiving study medication; 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
• 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; must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment
• Patient 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 which cannot be discontinued 2 weeks prior to day 1 of dosing and 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 substrates of CYP3A4, such as atorvastatin, simvastatin and lovastatin, is also prohibited in this study
• Herbal preparations are not allowed throughout the study; these herbal medications include but are not limited to: St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng; patients should stop using these herbal medications 7 days prior to first dose of study treatment
• Any known hypersensitivity or contraindication to the components of the study drug AZD1775
• 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)
• Mean resting corrected QTc interval using the Fridericia formula (QTcF) > 450 msec/male and > 470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
• Pregnant or breastfeeding women
• 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
• Symptomatic and uncontrolled metastasis in the central nervous system or leptomeningeal or lymphangitic carcinomatosis
• Presence of other active invasive cancers that do not harbor CCNE1 amplification
• Grade 2 or higher peripheral neuropathy
• Human immunodeficiency virus requiring highly active antiretroviral therapy (HAART) treatment due to unknown drug-drug interactions or has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive or C virus [e.g., hepatitis C virus (HCV) RNA (quantitative) is detected]) infection