AZD1775 for Advanced Solid Tumors

Inclusion Criteria

• •ELIGIBILITY CRITERIA:
• •Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed or for which standard therapies do not exist.
• •Patients must have measurable disease or evaluable disease for the escalation phase; for the 6 additional patients enrolled at maximum tolerated dose (MTD) for further evaluation of pharmacokinetics (PK) and pharmacodynamics (PD) endpoints (Expansion Cohort A). For the 6-patient breast cancer gene (BRCA)-mutation expansion cohort, patients must have measurable disease; however, tumor biopsies are optional. For Expansion Cohort B, patients must have tumor amenable to biopsy (excisional or incision biopsies of skin or head (H) \& neck (N) lesions under visualization) and willingness to undergo a tumor biopsy or patient will be undergoing a procedure due to medical necessity during which the tissue may be collected, or tumor biopsy tissue from a previous research study or medical care is available for submission at registration. Criteria for the submission of tissue are:
• •* Tissue must have been collected within 3 months prior to registration
• •* Patient has not received any intervening therapy for their cancer since the collection of the tumor sample
• •* Tumor tissue must meet the minimum requirements
• •Patients must have completed any chemotherapy, radiation therapy, surgery, or biologic therapy greater than or equal to 3 weeks (or \> 5 half-lives, whichever is shorter) prior to entering the study. Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in an exploratory Investigational New Drug (IND)/Phase 0 study or more than or equal to 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events.
• •Age greater than or equal to 18 years of age.
• •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky \>60%)
• •Life expectancy of greater than 3 months.
• •Patients must have normal organ and marrow function as defined below:
• •* leukocytes greater than or equal to 3,000/mcL
• •* absolute neutrophil count greater than or equal to 1,500/mcL
• •* platelets greater than or equal to 100,000/mcL
• •* hemoglobin \>9 g/dL
• •* total bilirubin less than or equal to 1.5 times institutional upper limit of normal
• •* Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) less than or equal to 3 times institutional upper limit of normal
• •* creatinine less than or equal to 1.5 times institutional upper limit of normal OR
• •* creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
• •The effects of Adavosertib (AZD1775) on the developing human fetus are unknown. For this reason and because molecular inhibitors of Wee1 kinase are known to be teratogenic, women of child-bearing potential (WoCBP) may be included only if acceptable contraception is in place for two weeks before study entry, for the duration of the treatment with the study drug, and for 2 months after the last dose of AZD1775. Male patients who are involved in the study must agree to avoid procreative and unprotected sex (i.e., by using acceptable forms of contraception) and must not donate sperm during the study and for 3 months after the last dose of AZD1775. Where the female partner is pregnant or not using effective birth control, men should be advised to abstain while in the study and for 3 months after the last dose of AZD1775. Female partners, who are of child-bearing potential, of men participating in clinical studies of AZD1775 will also be required to use effective contraceptive measures while their partner is on study drug and for 3 months thereafter. Male patients will be advised to arrange for the freezing of sperm samples prior to the start of the study should they wish to father children while on AZD1775 or during the 3 months after stopping AZD1775.
• •Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first of study drug and women should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
• •Patients must be able to swallow whole tablets or capsules. Nasogastric or G-tube administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed.
• •Ability to understand and the willingness to sign a written informed consent document.
• •Patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy.