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Protocol No. NCI10222

Principal Investigator Uboha, Nataliya

Phase II

Age Group Adult

Scope National

Sponsor Type Externally Peer-Reviewed

Title A Phase II study of olaparib and AZD6738 in isocitrate dehydrogenase (IDH) mutant solid tumors

Objective The purpose of this study is to test the good and bad effects of the drugs olaparib and AZD6738 in patients whose tumor has an abnormal gene called IDH1 or IDH2. Olaparib and AZD6738 could shrink your cancer, but they could also cause side effects, which are described in the risks section below. The study doctors hope to learn if the study drug will shrink the cancer by at least one quarter compared to its present size

Treatment Olaparib 300 mg every 12hrs each day of a 28-day cycle in tablet formation and AZD6738 160 mg everyday on days 1-7 of a 28-day cycle in tablet formation until disease progression, unacceptable toxicity, withdrawal of consent or death

Description A Phase II study of olaparib and AZD6738 in isocitrate dehydrogenase (IDH) mutant solid tumors

Key Eligibility
  • Must be diagnosed with a cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists. Patients with primary CNS tumors, e.g. glioma, are not allowed
  • Must have biopsy-confirmed evidence of an IDH1 or IDH2 mutation, confirmed in a CLIA-certified laboratory, associated with neomorphic activity of the encoded proteins
  • Must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies
  • Must have measurable disease by RECIST v1.1
  • Must have progressive cancer at the time of study entry
  • Prior experimental (non-FDA approved) therapies (other than drugs that target ATR) and immunotherapies are allowed. Patients must not have received these therapies for 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment
  • Treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period
  • Evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated. If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
  • 18 year of age or older
  • ECOG performance status 0-1
  • Adequate organ and bone marrow function as defined by the protocol
  • No features suggestive of MDS/AML on peripheral blood smear
  • Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol
  • Human immunodeficiency virus (HIV) on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
    EXCLUSION
  • Participation in another clinical study with an investigational product during the last 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment
  • Previous treatment with a PARP inhibitor, AZD6738 or any other ATR inhibitor
  • Receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
  • Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors
  • Myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
  • New or progressive brain metastases (active brain metastases) or leptomeningeal disease are not eligible if the treating physician determines that immediate CNS specific treatment is required
  • Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
  • Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable within the last 28 days)
  • Can not be pregnant or breastfeeding
  • Receiving, or having received during the 14 days prior to first dose, corticosteroids greater than 10 mg for any reason
  • Cardiac diseases as defined by the protocol
  • Risk of brain perfusion problems, e.g., medical history of carotid stenosis or pre-syncopal or syncopal episodes, history of TIAs
  • Uncontrolled hypertension (grade 2 or above) requiring clinical intervention
  • Relative hypotension (less than 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of greater than 20 mm Hg
  • Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of AZD6738

  • Applicable Disease Sites Anal; Any Site; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

    Status Open

    Participating Institutions UW Hospital and Clinics; UWCCC 1 South Park