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Protocol No. NCI10129

Principal Investigator Uboha, Nataliya

Phase II

Age Group Adult

Scope National

Sponsor Type Externally Peer-Reviewed

Title A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 mutant Advanced Solid Tumors

Objective The purpose of this study is to test any good and bad effects of a drug called Olaparib. Researchers showed in the laboratory that Olaparib can shrink tumors like yours or stop its growth. Olaparib has already been FDA approved to treat other cancers that have similar abnormalities. Researchers hope to learn if the study drug will shrink the cancer by at least one-quarter compared to its present size. Olaparib could shrink your cancer but it could also cause side effects

Treatment Patients in the cohort “IDH1/2 mutant cholangiocarcinoma” and “IDH1/2 mutant solid tumors” cohort will undergo a pre-treatment biopsy within 1 week (≤ 7 days) of starting therapy. Patients will take OLAPARIB 300 mg orally every 12 hours, 28 day cycles. Repeat biopsy will also be required at the time of first tumor assessment scan (8 weeks from the start of treatment). In the event of disease progression, a third biopsy will be required as long as the patient received a minimum of 1 Cycle of treatment following the second biopsy procedure

Description Phase 2 Study of PARP Inhibitor Olaparib(AZD2281) in IDH1 and IDH2 mutant Advanced Solid Tumors

Key Eligibility
  • Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists,with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins
  • Patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using an FDA-approved molecular test or a validated DNA-based assay conducted in a CLIA-certified laboratory
  • Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression)
  • Patients must be willing to undergo extra blood sampling for correlative studies
  • Subjects with extracranial disease must have evaluable disease by RECIST v1.1; subjects affected by glioma must have evaluable disease by RANO criteria
  • For subjects with glioma, specific inclusion criteria are required please contact study coordinator
  • Subjects must have progressive cancer at the time of study entry
  • Female/male of age greater than or equal to 18 years
  • ECOG 0-2, Karnofsky greater than or equal to 50%
  • Patients must have adequate organ and bone marrow function as described by the protocol
  • No features suggestive of MDS/AML on peripheral blood smear
  • Patients must have a life expectancy greater than or equal to 16 weeks
  • No previous treatment with the specific assigned study drug or any other PARP inhibitor
  • Prior radiation therapy is allowed, must not have received radiation therapy within 3 weeks prior to start of study
  • Women and Men of child-bearing potential are expected to use highly effective contraception as described by the protocol
    EXCLUSION
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
  • Resting ECG with QTc greater than 470 msec or family history of long QT syndrome
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inducers
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
  • Patients with symptomatic uncontrolled brain metastases
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
  • Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  • 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 as long as they received 28 days prior to study entry

  • 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