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Study of Ribociclib and Everolimus in HGG and DIPG

Primary Purpose

High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma

Status
Not yet recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ribociclib
Everolimus
Sponsored by
Nationwide Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Grade Glioma

Eligibility Criteria

12 Months - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

TarGeT-A study strata definitions Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D) Stratum B: Patients with DIPG Stratum C: Patients with primary thalamic, spinal cord, and/or secondary/radiation-related HGG. Stratum D: Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received CSI. Inclusion Criteria: Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on: 1.1) Age: patients must be ≥12 months and ≤30 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR: For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma (e.g., diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4. 1.3) Disease status: There are no disease status requirements for enrollment Patients without measurable disease are eligible. Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible Patients with a primary spinal HGG are eligible Patients with secondary, radiation-related HGG are eligible. Inclusion criteria for assignment to TarGeT-A, for all strata: 2.1) BSA ≥0.45m2 at the time of study entry. 2.2) Presence of at least one relevant actionable somatic alteration, detailed here: Pathogenic alterations presumed to cause activation of cell cycle: Amplification of CDK4 or CDK6 Deletion of CDKN2A, CDKN2B, or CDKN2C Amplification of CCND1 or CCND2 Pathogenic alterations presumed to cause activation of the PI3K/mTOR pathway: Deletion or mutation of PTEN Mutation or amplification of PIK3CA Mutation of PIK3R1 Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from this treatment protocol (TarGeT-A). Patients whose tumors harbor other alterations suspected to activate the cell cycle and/or PI3K/mTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee. 2.3) Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 2.4) Prior Therapy for HGG: Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible but discouraged. No other prior anticancer therapy for HGG will be allowed. Patients must have received photon or proton RT. Patients must have started RT within 31 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. RT delivered via photon or proton beam, must have been administered to a dose of within 10% of standard dosing (54 Gy for DIPG, 59.4 Gy for other HGG, XX for primary spinal disease, and/or XX Gy craniospinal for patients with spinal or leptomeningeal metastatic disease). Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT. 2.5) Organ Function Requirements 2.5.1) Adequate Bone Marrow Function Defined as: Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin >8 g/dL (may be transfused) 2.5.2) Adequate Renal Function Defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to < 2 years=0.6 mg/dL for males and females; 2 to < 6 years=0.8 mg/dL for males and females; 6 to < 10 years= 1.0 mg/dL for males and females; 10 to < 13 years=1.2 mg/dL for males and females. 13 to < 16 years=1.5 mg/dL for males and 1.4 mg/dL for females. 2.5.3) Adequate Liver Function Defined as: Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age AST(SGOT)/ALT(SGPT) ≤ 3 times institutional upper limit of normal Serum albumin ≥ 2g/dL 2.5.4) Adequate Cardiac Function Defined as: Ejection fraction of ≥ 50% by echocardiogram QTc ≤ 450 msec 2.5.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4/5. (Patients receiving enzyme inducing anti-epileptic drugs that are known strong inducers or inhibitors of CYP3A4/5 are not eligible) 2.5.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry >94% on room air if there is clinical indication for determination. 2.6) Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines Exclusion Criteria for All Strata: Pregnant or Breast-Feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods (hormonal or barrier method of birth control; abstinence) while being treated on this study and for 3 months after completing therapy. Concomitant Medications Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. Patients who are currently receiving another investigational drug are not eligible. Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only. Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4/5 are not eligible. Patients who are receiving strong inducers or inhibitors of CYP3A4/5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study. Patients who are receiving medications known to prolong QTc interval are not eligible. Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT < 1.5Xs ULN and INR < 1.5. Patients who have an uncontrolled infection are not eligible. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible. Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible. Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.

Sites / Locations

  • Children's Hospital Colorado
  • Children's National Medical Center
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Dana-Farber Cancer Institute
  • Duke University Health System
  • Cincinnati Children's Hospital Medical Center
  • Nationwide Children's Hospital
  • Children's Hospital of Philadelphia
  • Texas Children's Hospital
  • Seattle Children's Hospital
  • Sydney Children's Hospital
  • Queensland Children's Hospital
  • Perth Children's Hospital
  • The Hospital for Sick Children (SickKids)
  • Montreal Children's Hospital
  • Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
  • Princess Máxima Center
  • Great Ormond Street Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Stratum A (n=40)

Stratum B (n=40)

Stratum C (n=6-12)

Stratum D (n=6-12)

Arm Description

Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata B, C, or D).

Patients with DIPG, defined as a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (e.g., diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma).

Patients with primary thalamic, spinal cord, and/or secondary (radiation-related) HGG.

Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received craniospinal irradiation.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS) in HGG
To assess the efficacy of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with HGG (Stratum A) by estimating the distribution of PFS compared to molecularly-stratified and matched historical controls.
Overall Survival (OS) in DIPG
To assess the efficacy of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with DIPG (Stratum B) by estimating the distribution of OS compared to molecularly-stratified and matched historical controls.
Establish MTD and RP2D of ribociclib and everolimus
To identify the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of the combination of ribociclib and everolimus given to patients with metastatic HGG who have received craniospinal irradiation CSI (stratum D).

Secondary Outcome Measures

Overall Survival in HGG
Determine distribution of OS for pediatric and young adult patients newly-diagnosed with HGG which harbor cell cycle and/or PI3K/mTOR pathway alterations treated with post-RT ribociclib and everolimus.
Objective Response Rate (ORR) in HGG
Evaluate the radiographic objective response rate (ORR) defined as complete response (CR) + partial response (PR) in pediatric and young adult patients newly diagnosed with HGG treated with the combination of ribociclib and everolimus.
Objective Response Rate (ORR) in DIPG
Evaluate the radiographic objective response rate (ORR) defined as complete response (CR) + partial response (PR) in pediatric and young adult patients newly diagnosed with DIPG treated with the combination of ribociclib and everolimus.
Number of participants with ribociclib and everolimus-related adverse events as assessed by CTCAE v5.0
Assess and further characterize the safety and toxicity of post-RT combination of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with HGG, including DIPG. This will be achieved by calculating the number of participants with, as well as frequency and severity of, ribociclib and everolimus-related Adverse Events as assessed by CTCAE v5.0.
Evaluate Health-Related Quality of Life Outcomes
Evaluate health-related quality of life outcomes of pediatric and young adult patients newly-diagnosed with HGG, including DIPG, treated with combination of ribociclib and everolimus, by patient and/or parent reporting at key timepoints in therapy using the patient reported outcomes measurement information system (PROMIS) survey.

Full Information

First Posted
April 20, 2023
Last Updated
September 27, 2023
Sponsor
Nationwide Children's Hospital
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT05843253
Brief Title
Study of Ribociclib and Everolimus in HGG and DIPG
Official Title
PhaseII Study of Ribociclib and Everolimus Following Radiotherapy in Pediatric and Young Adult Patients Newly Diagnosed With HGG Including DIPG, Which Harbor Alterations of the Cell Cycle and/or PI3K/mTOR Pathways
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 15, 2024 (Anticipated)
Primary Completion Date
January 15, 2028 (Anticipated)
Study Completion Date
January 15, 2034 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nationwide Children's Hospital
Collaborators
Novartis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this study is to determine the efficacy of the study drugs ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K/mTOR) that these drugs target. The main question the study aims to answer is whether the combination of ribociclib and everolimus can prolong the life of patients diagnosed with HGG, including DIPG.
Detailed Description
This is a multicenter, international, phase II study of post-radiotherapy (RT) combination of ribociclib and everolimus to treat pediatric, adolescent, and young adult patients newly diagnosed with HGG and DIPG that harbor alterations of the cell cycle and/or PI3K/mTOR pathways to assess treatment efficacy. Efficacy is defined by progression-free survival (PFS; HGG [stratum A]) and Overall Survival (OS; DIPG [stratum B]), with key longitudinal biomarker correlatives. Outcomes among patients with primary thalamic, spinal cord, and/or secondary (radiation related) HGG (strata C) will be descriptively analyzed. Objective radiographic response rates and agent-specific toxicities will also be assessed, with a feasibility cohort to determine the recommended phase II dose (RP2D) of the combination of ribociclib and everolimus in patients with metastatic disease who received upfront craniospinal irradiation (stratum D) Protocol therapy with the maintenance combination of ribociclib and everolimus must begin no later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT. Each cycle will be 28 days in duration and treatment can continue up to a total of 26 cycles. Ribociclib will be given orally once daily for 3 weeks (days 1-21), with one week off. Everolimus will be given orally daily continuously (days 1-28).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Glioblastoma, Glioblastoma Multiforme, Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Brain Tumor, WHO Grade III Glioma, WHO Grade IV Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Ribociclib and Everolimus
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Stratum A (n=40)
Arm Type
Experimental
Arm Description
Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata B, C, or D).
Arm Title
Stratum B (n=40)
Arm Type
Experimental
Arm Description
Patients with DIPG, defined as a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (e.g., diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma).
Arm Title
Stratum C (n=6-12)
Arm Type
Experimental
Arm Description
Patients with primary thalamic, spinal cord, and/or secondary (radiation-related) HGG.
Arm Title
Stratum D (n=6-12)
Arm Type
Experimental
Arm Description
Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received craniospinal irradiation.
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Other Intervention Name(s)
Kisqali
Intervention Description
Ribociclib PO qd on days 1-21
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Intervention Description
Everolimus PO qd on days 1-28
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) in HGG
Description
To assess the efficacy of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with HGG (Stratum A) by estimating the distribution of PFS compared to molecularly-stratified and matched historical controls.
Time Frame
From date on treatment until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up to 60 months
Title
Overall Survival (OS) in DIPG
Description
To assess the efficacy of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with DIPG (Stratum B) by estimating the distribution of OS compared to molecularly-stratified and matched historical controls.
Time Frame
From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
Title
Establish MTD and RP2D of ribociclib and everolimus
Description
To identify the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of the combination of ribociclib and everolimus given to patients with metastatic HGG who have received craniospinal irradiation CSI (stratum D).
Time Frame
Completion of Cycle 1 (28 days)
Secondary Outcome Measure Information:
Title
Overall Survival in HGG
Description
Determine distribution of OS for pediatric and young adult patients newly-diagnosed with HGG which harbor cell cycle and/or PI3K/mTOR pathway alterations treated with post-RT ribociclib and everolimus.
Time Frame
From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
Title
Objective Response Rate (ORR) in HGG
Description
Evaluate the radiographic objective response rate (ORR) defined as complete response (CR) + partial response (PR) in pediatric and young adult patients newly diagnosed with HGG treated with the combination of ribociclib and everolimus.
Time Frame
From Day 1 of protocol treatment through 30 days following end of protocol treatment
Title
Objective Response Rate (ORR) in DIPG
Description
Evaluate the radiographic objective response rate (ORR) defined as complete response (CR) + partial response (PR) in pediatric and young adult patients newly diagnosed with DIPG treated with the combination of ribociclib and everolimus.
Time Frame
From Day 1 of protocol treatment through 30 days following end of protocol treatment
Title
Number of participants with ribociclib and everolimus-related adverse events as assessed by CTCAE v5.0
Description
Assess and further characterize the safety and toxicity of post-RT combination of ribociclib and everolimus in pediatric and young adult patients newly diagnosed with HGG, including DIPG. This will be achieved by calculating the number of participants with, as well as frequency and severity of, ribociclib and everolimus-related Adverse Events as assessed by CTCAE v5.0.
Time Frame
From Day 1 of protocol treatment through 30 days following end of protocol treatment
Title
Evaluate Health-Related Quality of Life Outcomes
Description
Evaluate health-related quality of life outcomes of pediatric and young adult patients newly-diagnosed with HGG, including DIPG, treated with combination of ribociclib and everolimus, by patient and/or parent reporting at key timepoints in therapy using the patient reported outcomes measurement information system (PROMIS) survey.
Time Frame
At the end of Cycles 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
TarGeT-A study strata definitions Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D) Stratum B: Patients with DIPG Stratum C: Patients with primary thalamic, spinal cord, and/or secondary/radiation-related HGG. Stratum D: Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received CSI. Inclusion Criteria: Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on: 1.1) Age: patients must be ≥12 months and ≤30 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR: For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma (e.g., diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4. 1.3) Disease status: There are no disease status requirements for enrollment Patients without measurable disease are eligible. Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible Patients with a primary spinal HGG are eligible Patients with secondary, radiation-related HGG are eligible. Inclusion criteria for assignment to TarGeT-A, for all strata: 2.1) BSA ≥0.45m2 at the time of study entry. 2.2) Presence of at least one relevant actionable somatic alteration, detailed here: Pathogenic alterations presumed to cause activation of cell cycle: Amplification of CDK4 or CDK6 Deletion of CDKN2A, CDKN2B, or CDKN2C Amplification of CCND1 or CCND2 Pathogenic alterations presumed to cause activation of the PI3K/mTOR pathway: Deletion or mutation of PTEN Mutation or amplification of PIK3CA Mutation of PIK3R1 Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from this treatment protocol (TarGeT-A). Patients whose tumors harbor other alterations suspected to activate the cell cycle and/or PI3K/mTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee. 2.3) Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 2.4) Prior Therapy for HGG: Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible but discouraged. No other prior anticancer therapy for HGG will be allowed. Patients must have received photon or proton RT. Patients must have started RT within 31 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery. RT delivered via photon or proton beam, must have been administered to a dose of within 10% of standard dosing (54 Gy for DIPG, 59.4 Gy for other HGG, XX for primary spinal disease, and/or XX Gy craniospinal for patients with spinal or leptomeningeal metastatic disease). Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT. 2.5) Organ Function Requirements 2.5.1) Adequate Bone Marrow Function Defined as: Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin >8 g/dL (may be transfused) 2.5.2) Adequate Renal Function Defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to < 2 years=0.6 mg/dL for males and females; 2 to < 6 years=0.8 mg/dL for males and females; 6 to < 10 years= 1.0 mg/dL for males and females; 10 to < 13 years=1.2 mg/dL for males and females. 13 to < 16 years=1.5 mg/dL for males and 1.4 mg/dL for females. 2.5.3) Adequate Liver Function Defined as: Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age AST(SGOT)/ALT(SGPT) ≤ 3 times institutional upper limit of normal Serum albumin ≥ 2g/dL 2.5.4) Adequate Cardiac Function Defined as: Ejection fraction of ≥ 50% by echocardiogram QTc ≤ 450 msec 2.5.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4/5. (Patients receiving enzyme inducing anti-epileptic drugs that are known strong inducers or inhibitors of CYP3A4/5 are not eligible) 2.5.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry >94% on room air if there is clinical indication for determination. 2.6) Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines Exclusion Criteria for All Strata: Pregnant or Breast-Feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods (hormonal or barrier method of birth control; abstinence) while being treated on this study and for 3 months after completing therapy. Concomitant Medications Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported. Patients who are currently receiving another investigational drug are not eligible. Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only. Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4/5 are not eligible. Patients who are receiving strong inducers or inhibitors of CYP3A4/5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study. Patients who are receiving medications known to prolong QTc interval are not eligible. Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT < 1.5Xs ULN and INR < 1.5. Patients who have an uncontrolled infection are not eligible. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible. Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible. Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leonie Mikael, PhD
Phone
16147223284
Email
leonie.mikael@nationwidechildrens.org
First Name & Middle Initial & Last Name or Official Title & Degree
Dorothy Crabtree, BS
Phone
16147228693
Email
Dorothy.Crabtree@nationwidechildrens.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margot Lazow, MD
Organizational Affiliation
Nationwide Children's Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Maryam Fouladi, MD
Organizational Affiliation
Nationwide Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathleen Dorris, MD
Phone
720-777-8314
Email
kathleen.dorris@childrenscolorado.org
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Hwang, MD
Phone
202-476-5046
Email
ehwang@childrensnational.org
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Plant, MD
Phone
312-227-4090
Email
Aplant@luriechildrens.org
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Chi, MD
Phone
617-632-4386
Email
Susan_chi@dfci.harvard.edu
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Ashley, MD
Phone
919-681-3824
Email
david.ashley@duke.edu
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter de Blank, MD
Phone
513-517-2068
Email
Peter.deBlank@cchmc.org
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maryam Fouladi, MD
Phone
614-722-5758
Email
Maryam.fouladi@nationwidechildrens.org
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael J Fisher, MD
Phone
215-590-5188
Email
fisherm@email.chop.edu
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Baxter, MD
Phone
832-824-4681
Email
pabaxter@txch.org
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Leary, MD
Phone
206-987-2106
Email
sarah.leary@seattlechildrens.org
Facility Name
Sydney Children's Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Ziegler, MBBS
Phone
+61293821730
Email
d.ziegler@unsw.edu.au
Facility Name
Queensland Children's Hospital
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tim Hassall, MBBS
Phone
+61730683593
Email
tim.hassall@health.qld.gov.au
Facility Name
Perth Children's Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Gottardo, MBChB
Phone
+61864560241
Email
nick.gottardo@health.wa.gov.au
Facility Name
The Hospital for Sick Children (SickKids)
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X8
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Bouffet, MD
Phone
4168137457
Email
eric.bouffet@sickkids.ca
Facility Name
Montreal Children's Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Genevieve Legault, MD
Phone
5144124400
Ext
60497
Email
Genevieve.legault4@mcgill.ca
Facility Name
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69120
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olaf Witt, MD
Phone
0496221423570
Email
o.witt@kitz-heidelberg.de
Facility Name
Princess Máxima Center
City
Utrecht
ZIP/Postal Code
3720
Country
Netherlands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jasper van der Lugt, MD, PhD
Phone
31 6 18559694
Email
D.G.vanVuurden@prinsesmaximacentrum.nl
Facility Name
Great Ormond Street Hospital
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Hargrave, MD
Phone
02078138525
Email
darren.hargrave@nhs.net

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Ribociclib and Everolimus in HGG and DIPG

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