Trial Search Results

Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that have spread to other places in the body and usually cannot be cured or controlled with treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: Olaparib

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Subjects must be able to understand the nature of this trial and provide written
   informed consent, prior to any study specific procedures; patients with Impaired
   Decision Making Capacity (IDMC) who have a close caregiver or legally authorized
   representative (LAR) may be considered eligible for this study at the treating
   physician's discretion, provided that the physician is reasonably sure that the
   possible risks and benefits of the study are clear and that the patient will take the
   drug as prescribed

   - 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 a Food and
   Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid
   (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments
   (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic
   phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S,
   R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K

   - 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); in case of multiple lesions, tumor biopsies will be performed on the
   most accessible site of disease; all possible precautions to avoid complications will
   be taken, including discussions in multidisciplinary meetings, if needed; patients
   affected by glioma will not be considered for study biopsies

   - Patients must be willing to undergo extra blood sampling for correlative studies

   - Subjects with extracranial disease must have evaluable disease by Response Evaluation
   Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must
   have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO)
   criteria

   - For subjects with glioma, specific inclusion criteria are as follows:

      - The disease should be recurrent or transformed glioma; subjects must not have had
      prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment

      - There must be an enhancing component of disease, as evaluated on pre-treatment
      magnetic resonance imaging (MRI)

      - For patients with World Health Organization (WHO) grade III or IV glioma and
      progressive disease < 12 weeks after completion of chemoradiotherapy, progression
      can be defined by the following set of criteria:

         - New enhancement outside of the radiation field (beyond the high-dose region
         or 80% isodose line)

         - If there is unequivocal evidence of viable tumor on histopathologic sampling
         (e.g., solid tumor areas. i.e., > 70% tumor cell nuclei in areas), high or
         progressive increase in MIB-1 proliferation index compared with prior
         biopsy, or evidence for histologic progression or increased anaplasia in
         tumor);

         - Note: Given the difficulty of differentiating true progression from
         pseudoprogression, clinical decline alone, in the absence of radiographic or
         histologic confirmation of progression, will not be sufficient for
         definition of progressive disease in the first 12 weeks after completion of
         concurrent chemoradiotherapy

      - For patients with WHO grade III or IV glioma and progressive disease >= 12 weeks
      after completion of chemoradiotherapy, progression can be defined by the
      following set of criteria:

         - New contrast-enhancing lesion outside of radiation field on decreasing,
         stable, or increasing doses of corticosteroids

         - Increase by >= 25% in the sum of the products of perpendicular diameters
         between the first post-radiotherapy scan, or a subsequent scan with smaller
         tumor size, and the scan at 12 weeks or later on stable or increasing doses
         of corticosteroids

         - For patients receiving antiangiogenic therapy, significant increase in
         T2/fluid attenuated inversion recovery (FLAIR) non-enhancing lesion may also
         be considered progressive disease; the increased T2/FLAIR must have occurred
         with the patient on stable or increasing doses of corticosteroids compared
         with baseline scan or best response after initiation of therapy and not be a
         result of comorbid events (e.g., effects of radiation therapy,
         demyelination, ischemic injury, infection, seizures, postoperative changes,
         or other treatment effects)

         - Note: Clinical deterioration alone is not attributable to concurrent
         medication or comorbid conditions is sufficient to declare progression on
         current treatment but not for entry onto a clinical trial for recurrence

      - For patients with WHO grade II glioma progression is defined by any one of the
      following:

         - Development of new lesions or increase of enhancement (radiological evidence
         of malignant transformation)

         - A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or
         increasing doses of corticosteroids compared with baseline scan or best
         response after initiation of therapy, not attributable to radiation effect
         or to comorbid events

   - For subject with extracranial disease, they must have at least one lesion, not
   previously irradiated, that can be accurately measured at baseline as >= 10 mm in the
   longest diameter (except lymph nodes which must have short axis >= 15 mm) with
   computed tomography (CT) or magnetic resonance imaging (MRI) or >= 10 mm with calipers
   by clinical exam OR at least one lesion (measurable and/or non-measurable) that can be
   accurately assessed by CT/MRI/pain x-ray/clinical exam at baseline and follow up
   visits

   - Subjects must have progressive cancer at the time of study entry; prior experimental
   (non-FDA approved) therapies (other than drugs that share the same target) 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; toxicities from these therapies should have recovered to =< grade 1,
   with the exception of stable chronic grade 2 that is not overlapping with presumed
   toxicities of olaparib

   - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 50%)

   - Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days
   prior to administration of study treatment)

   - Leukocytes >= 3,000/mcL (within 28 days prior to administration of study treatment)

   - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to
   administration of study treatment)

   - Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study
   treatment)

   - Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days
   prior to administration of study treatment)

   - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
   [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
   =< 2.5 x institutional upper limit of normal unless liver metastases are present in
   which case they must be =< 5 x ULN (within 28 days prior to administration of study
   treatment)

   - Creatinine clearance estimated using the Cockcroft-Gault equation of >= 51 mL/min
   (within 28 days prior to administration of study treatment)

   - Patients must have a life expectancy >= 16 weeks

   - Patient is willing and able to comply with the protocol for the duration of the study
   including undergoing treatment and scheduled visits and examinations including follow
   up

   - No previous treatment with the specific assigned study drug or any other PARP
   inhibitor

   - Prior radiation therapy is allowed; patients must not have received radiation therapy
   within 3 weeks prior to the initiation of study treatment

   - Women of child-bearing potential are expected to use highly effective contraception
   during the study and for 1 month after the last dose of study drug; postmenopausal or
   evidence of non-childbearing status for women of childbearing potential: negative
   urine or serum pregnancy test within 28 days of study treatment and confirmed prior to
   treatment on day 1; postmenopausal is defined as one or more of the following:

      - Amenorrheic for 1 year or more following cessation of exogenous hormonal
      treatments

      - Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the
      post-menopausal range for women under 50

      - Radiation-induced oophorectomy with last menses > 1 year ago

      - Chemotherapy-induced menopause with > 1 year interval since last menses

      - Surgical sterilization (bilateral oophorectomy or hysterectomy)

   - Male patients and their partners, who are sexually active and of childbearing
   potential, must agree to the use of two highly effective forms of contraception in
   combination, throughout the period of taking study treatment and for 3 months after
   last dose of study drug(s) to prevent pregnancy in a partner

Exclusion Criteria:

   - Patients should not enter the study if any of the following exclusion criteria are
   fulfilled

   - Involvement in the planning and/or conduct of the study

   - Previous enrollment in the present study

   - 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 (6 weeks for nitrosoureas or mitomycin C)

   - Any previous treatment with PARP inhibitor, including olaparib

   - Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
   reasons) within 3 weeks prior to study treatment

   - Other malignancy within the last 5 years except: adequately treated non-melanoma skin
   cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ
   (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including
   lymphomas (without bone marrow involvement) curatively treated with no evidence of
   disease for >= 5 years; patients with a history of localized triple negative breast
   cancer may be eligible, provided they completed their adjuvant chemotherapy more than
   three years prior to registration, and that the patient remains free of recurrent or
   metastatic disease

   - Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec or family
   history of long QT syndrome

   - Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin,
   clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
   saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.
   ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout
   period prior to starting olaparib is 2 weeks; because the lists of these agents are
   constantly changing, it is important to regularly consult a frequently updated drug
   information reference; medical reference texts such as the Physicians' Desk Reference
   may also provide this information; as part of the enrollment/informed consent
   procedures, the patient will be counseled on the risk of interactions with other
   agents, and what to do if new medications need to be prescribed or if the patient is
   considering a new over-the-counter medicine or herbal product

   - Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin,
   rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or
   moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout
   period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
   weeks for other agents; because the lists of these agents are constantly changing, it
   is important to regularly consult a frequently updated drug information reference;
   medical reference texts such as the Physicians' Desk Reference may also provide this
   information; as part of the enrollment/informed consent procedures, the patient will
   be counseled on the risk of interactions with other agents, and what to do if new
   medications need to be prescribed or if the patient is considering a new
   over-the-counter medicine or herbal product

   - Persistent toxicities caused by previous cancer therapy; toxicities should have
   recovered to =< grade 1, excluding alopecia and stable chronic grade 2 toxicity that
   is not overlapping with presumed toxicities of olaparib

   - Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
   suggestive of MDS/AML

   - Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence
   of brain metastases is not required; the patient can receive a stable dose of
   corticosteroids before and during the study if these were started at least 4 weeks
   prior to treatment; patients with spinal cord compression unless considered to have
   received definitive treatment for this and evidence of clinically stable disease for
   28 days; patients with known uncontrolled brain metastases should be excluded from
   this clinical trial because of their poor prognosis and because they often develop
   progressive neurologic dysfunction that would confound the evaluation of neurologic
   and other adverse events

   - Major surgery within 2 weeks of starting study treatment; effects from surgeries
   should have recovered to =< grade 1, with the exception of stable chronic grade 2 that
   is not overlapping with presumed toxicities of olaparib

   - Patients considered a poor medical risk due to a serious, uncontrolled medical
   disorder, non-malignant systemic disease or active, uncontrolled infection; examples
   include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
   months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
   cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
   disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder
   that prohibits obtaining informed consent and would limit compliance with study
   requirements

   - Patients unable to swallow orally administered medication and patients with
   gastrointestinal disorders likely to interfere with absorption of the study medication

   - Women who are actively breast feeding

   - Immunocompromised patients, e.g., patients who are known to be serologically positive
   for human immunodeficiency virus (HIV); HIV-positive patients on combination
   antiretroviral therapy are ineligible because of the potential for pharmacokinetic
   interactions with Olaparib; in addition, these patients are at increased risk of
   lethal infections when treated with marrow-suppressive therapy; appropriate studies
   will be undertaken in patients receiving combination antiretroviral therapy when
   indicated

   - Patients with a known hypersensitivity to olaparib or any of the excipients of the
   product; history of allergic reactions attributed to compounds of similar chemica

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jee Min Lee
650-497-5240
Recruiting