A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma
- Conditions
- High Grade GliomaDiffuse Intrinsic Pontine Glioma
- Registration Number
- NCT03605550
- Lead Sponsor
- Nationwide Children's Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 64
Inclusion Criteria:<br><br>Age: Patients must be =12 months and = 21 years of age at the time of study enrollment.<br><br>Diagnosis: Patients with newly-diagnosed diffuse intrinsic pontine gliomas (DIPGs),<br>defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the<br>pons, are eligible without histologic confirmation.<br><br>Patients with brainstem tumors that do not meet radiographic criteria or are not<br>considered to be typical diffuse intrinsic pontine gliomas will be eligible if the tumors<br>are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma,<br>glioblastoma, H3K27-mutant diffuse midline glioma) or diffuse astrocytoma.<br><br>Patients with newly-diagnosed non-brainstem high-grade glioma (HGG) are eligible.<br><br>Patients must have had histologically verified high-grade glioma such as anaplastic<br>astrocytoma, glioblastoma, H3 K27 mutant diffuse midline glioma etc.<br><br>Patients eligible for the surgical stratum include patients with:<br><br> 1. Newly-diagnosed DIPG who are amenable to undergo biopsy at the recommendation of<br> their treating physician<br><br> 2. Newly-diagnosed HGG for whom a second surgical resection is warranted for further<br> debulking or to achieve a near-total or gross total resection after initial<br> diagnosis has been made but prior to start of therapy.<br><br> Disease Status: Patients with disseminated DIPG or HGG are not eligible, and MRI of<br> spine must be performed if disseminated disease is suspected clinically by the<br> treating physician.<br><br> Performance Level: Karnofsky = 50 for patients > 16 years of age and Lansky = 50 for<br> patients = 16 years of age. Patients who are unable to walk because of paralysis,<br> but who are up in a wheelchair, will be considered ambulatory for the purpose of<br> assessing the performance score.<br><br> Neurologic Status: Patients must be able to swallow oral medications to be eligible<br> for study enrollment.<br><br> Patients enrolling on Part A (phase I, capsule formulation) must be able to swallow<br> whole capsules.<br><br> Prior Therapy: Patients must not have received any prior anticancer therapy. Prior<br> dexamethasone and/or surgery are permissible.<br><br> Organ Function Requirements:<br><br> Adequate Bone Marrow Function Defined as:<br><br> • Peripheral absolute neutrophil count (ANC) = 1000/mm3<br><br> • Platelet count = 100,000/mm3 (transfusion independent, defined as not receiving<br> platelet transfusions for at least 7 days prior to enrollment)<br><br> • Hemoglobin >8 g/dL (may be transfused).<br><br> Adequate Renal Function Defined as:<br><br> • Creatinine clearance or radioisotope GFR = 70ml/min/1.73 m2 or<br><br> • A serum creatinine based on age/gender as follows:<br><br> - 1 to < 2 years: 0.6 (Male) 0.6 (Female)<br><br> - 2 to < 6 years: 0.8 (Male) 0.8 (Female)<br><br> - 6 to < 10 years: 1 (Male) 1 (Female)<br><br> - 10 to < 13 years: 1.2 (Male) 1.2 (Female)<br><br> - 13 to < 16 years: 1.5 (Male) 1.4 (Female)<br><br> - 16 years: 1.7 (Male) 1.4 (Female)<br><br> Adequate Liver Function Defined as:<br><br> • Total bilirubin must be = 1.5 times institutional upper limit of normal for age<br><br> • AST(SGOT)/ALT(SGPT) < 3 times institutional upper limit of normal<br><br> • Serum albumin = 2g/dL<br><br> Adequate Cardiac Function Defined As:<br><br> - Ejection fraction of = 55% by echocardiogram.<br><br> - QTc = 480 msec.<br><br> Adequate Pulmonary Function Defined as<br><br> - No evidence of dyspnea at rest, and a pulse oximetry > 94% in room air if there<br> is clinical indication for determination<br><br> Adequate Neurologic Function Defined as:<br><br> - Patients with seizure disorder may be enrolled if on anticonvulsants and well<br> controlled.<br><br> Informed Consent: All patients and/or their parents or legally authorized<br> representatives must sign a written informed consent. Assent, when appropriate, will<br> be obtained according to institutional guidelines.<br><br> Exclusion Criteria:<br><br> Diagnosis: patients with a diagnosis of oligodendroglioma or oligoastrocytoma are<br> not eligible. Patients with juvenile pilocytic astrocytoma, are not eligible.<br><br> Patients with non-brainstem diffuse astrocytoma (grade 2) are not eligible for the<br> HGG stratum of the study.<br><br> Pregnancy or breast-feeding: Pregnant or breast-feeding women will not be entered on<br> this study due to known or unknown risks of fetal and teratogenic adverse events as<br> seen in animal/human studies. Pregnancy tests must be obtained in girls who are<br> post-menarchal. Males or females of reproductive potential may not participate<br> unless they have agreed to use an effective contraceptive method.<br><br> Patients of childbearing or child fathering potential must agree to use adequate<br> contraceptive methods (hormonal or barrier method of birth control; abstinence)<br> while being treated on this study and for 3 months after completing therapy. Note:<br> The definition of effective contraception will be based on the judgment of the<br> principal investigator or a designated associate.<br><br> Concomitant Medications<br><br> - Corticosteroids: Patients receiving corticosteroids are eligible. The use of<br> corticosteroids must be reported.<br><br> - Investigational Drugs: Patients who are currently receiving another<br> investigational drug are not eligible.<br><br> - Anti-cancer Agents: Patients who are currently receiving other anti-cancer<br> agents are not eligible.<br><br> - Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants as<br> listed in appendix II, are not eligible<br><br> - Patients who are receiving rifampin are not eligible.<br><br> - Patients who are receiving medications known to prolong QTc interval as listed<br> in appendix III are not eligible.<br><br> - Patients who are receiving duloxetine, alosetron or theophylline (CYP1A2<br> inhibitors) are not eligible<br><br> - Patients on beta-blockers are not eligible<br><br> - Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa),<br> escitalopram (Lexapro), Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine<br> (Paxil), sertraline (Zoloft) should be used with caution but are not<br> contraindicated.<br><br> - Anticoagulants: patients who are receiving therapeutic anticoagulants including<br> warfarin, low-molecular weight heparin are not eligible<br><br> Nasogastric or G tube administration of PTC596 is not permissible.<br><br> Infection: Patients who have an uncontrolled infection are not eligible.<br><br> Patients who, in the opinion of the investigator, may not be able to comply with the<br> safety monitoring requirements of the study are not eligible.<br><br> Patients with evidence of bowel obstruction, malabsorption, or other<br> contraindication to oral medication are not eligible.<br><br> Patients with GI disease or other condition that could affect absorption or<br> predispose subject to gastrointestinal ulceration are not eligible.<br><br> Patients with an active peptic ulcer disease or inflammatory bowel disease<br> (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis,<br> symptomatic cholangitis or appendicitis are not eligible.<br><br> Patients with serious non-healing
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Establish MTD and RP2D of PTC596;Number of participants with treatment-related adverse events as assessed by CTCAE v5.0;Maximum Plasma Concentration [Cmax] of PTC596 (A, B, C, D);Tumor Concentration of PTC596 (B);Protein levels of BMI1 in tumor
- Secondary Outcome Measures
Name Time Method Evaluate Overall survival;Evaluate Progression Free survival