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COZMOS:Phase I/Ib Trial of Combined 5'Azacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain/Solid Tumors (COZMOS)

Primary Purpose

Recurrent Childhood CNS Tumor, Ependymoma, Recurrent Childhood, Childhood Solid Tumor

Status
Unknown status
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
5 Azacytidine
Sponsored by
The Hospital for Sick Children
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Childhood CNS Tumor

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Greater than the age of 1 year and under age 18 at the time of study enrolment
  2. Recurrent or refractory brain or solid tumor, including recurrent or refractory ependymoma
  3. Tissue from diagnosis or resection prior to registration must be available (either flash frozen tissue or an FFPE block)
  4. Previous therapy with carboplatin will be permitted
  5. Failed first line treatment (surgery, radiation therapy or chemotherapy) and should not be eligible for treatment with curative potential.
  6. Be at least 4 weeks from the completion of myelosuppressive chemotherapy and/or biologic agents before starting day 1 of this study treatment
  7. Be at least 14 days from the completion of radiation therapy and MIBG before starting day 1 of this study treatment
  8. Be at least 3 months post hematopoetic stem cell rescue following myeloablative therapy before starting day 1 of this study treatment
  9. Must have visible disease on imaging. Resection of visible disease is permitted while on study after two cycles including achievement of a gross total resection. If a resection is performed while on study, fresh frozen tissue should be submitted for analysis.
  10. Concurrent medications will be limited to supportive medications/agents including but not limited to anti-emetics, steroids, analgesics and non-enzyme inducing anticonvulsants. Strong inducers of the P450 system will not be permitted. Other concurrent medications require approval of the study Sponsor.
  11. Ability of the parent and/or child to understand and the willingness to sign a written informed consent document
  12. Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I for the Karnofsky-Lansky Scores). 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. Patients with posterior fossa syndrome/cerebellar mutism demonstrating clear improvement post-surgically can be enrolled based on physician discretion
  13. Adequate hepatic, renal, marrow and cardiac function as defined below within 28 days prior to cycle 1 day 1:

    • Serum creatinine within normal institutional limits or creatinine clearance greater than 60mL/min
    • Serum bilirubin <1.5 times upper limit of institutional normal. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis
    • AST, ALT and Alkaline Phosphatase <3 times upper limit of institutional normal. If liver metastases are present, then <5 times upper limit of normal is permitted.
    • Normal QTc interval at screening ECG (baseline echocardiogram is not required)
    • Adequate marrow function defined below within 14 days prior to cycle 1 day 1:

      • Leukocytes greater than or equal to 1000 x106/L
      • Absolute neutrophil count greater than or equal to 0.75 x109/L
      • Platelets greater than or equal to 75 x109/L
      • Hemoglobin greater than or equal to 10g/dL (may be transfused).

Exclusion Criteria:

  1. Female patient who is pregnant or breast feeding (Lactating females must agree not to breast feed while taking azacitidine) or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 6 months after the end of study treatment.
  2. Patients may not be receiving any other investigational agents within 30 days prior to day 1 of protocol treatment
  3. Prior therapy with a DNA demethylase inhibitor
  4. Evidence of cardiac toxicity (shortening fraction below 28%; shortening fraction measures and ratios the change in the diameter of the left ventricle between the contracted and relaxed states)
  5. Abnormal coagulation parameters (PT >15 seconds, PTT>40 seconds, and/or INR >1.5)
  6. Significant active cardiac disease within the previous 6 months including:

    • NYHA class 3 or 4 CHF
    • Unstable angina
    • Myocardial infarction
  7. Known or suspected hypersensitivity to azacitidine or mannitol carboplatin
  8. Previous carboplatin exposure is not an exclusion criteria but previous allergic reaction to carboplatin will exclude enrolment.
  9. Patient must not require use of enzyme inducing anticonvulsants; patients who are receiving an enzyme inducing anticonvulsant must be able to switch to a non-enzyme inducing anticonvulsant such as Levetiracetam, Clobazam, Lacosamide, Valproate or Topiramate at least 2 weeks prior to study enrolment.
  10. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
  11. Active viral infection with HIV or hepatitis type B or C Patients with advanced malignant hepatic tumors
  12. Patients with advanced malignant hepatic tumors

Sites / Locations

  • Children's National Medical Center
  • Royal Children's Hospital Melbourne
  • Women's and Children's Hospital
  • Monash Children's Hospital
  • John Hunter Children's Hospital
  • Perth Children's Hospital
  • Queensland Children's Hospital
  • Sydney Children's Hospital
  • Children's Hospital at Westmead
  • Alberta Children's Hospital
  • BC Children's Hospital
  • McMaster Children's Hospital
  • London Health Sciences Centre
  • Children's Hospital of Eastern Ontario
  • Hospital for Sick Children
  • Centre hospitalier universitaire Sainte-Justine
  • Montreal Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase I Dose-escalation

Posterior Fossa Ependymoma Expansion Arm

Recurrent Brain and Solid Tumour Expansion Arm

Arm Description

5'azacytidine will be administered on Days 1-7 at a dose of 75mg/m2/day, followed by escalating doses of Carboplatin on Day 14 in a rolling 6 design. Carboplatin will be dosed initially at AUC 4. Dose level -1 will reduce 5'azacytidine to 50mg/m2/day.

5'azacytidine will be administered on days 1-7 and carboplatin will be administered on day 14 at the maximum tolerated dose achieved in the Phase I dose escalation to 20 patients with recurrent/refractory posterior fossa ependymoma.

5'azacytidine will be administered on days 1-7 and carboplatin will be administered on day 14 at the maximum tolerated dose achieved in the Phase I dose escalation up to 12 patients with recurrent/refractory brain and solid tumour.

Outcomes

Primary Outcome Measures

Establish maximum tolerated dose of carboplatin in combination with 5'azacytidine
Number of participants with treatment-related adverse events as assessed by the CTCAE4.0

Secondary Outcome Measures

Characterization of the pharmacodynamics of 5'-azacitidine in combination with carboplatin
Plasma pharmacodynamics will be assessed using methylation profiling of whole blood collected before and after administration of 5'Azacytidine, and after administration of carboplatin.
Assessment of intratumoral DNA demethylation as a preliminary indication of biological efficacy of this combination.
Where feasible, two cycles of 5'azacytidine and carboplatin will be administered prior to a biopsy and/or gross total resection, and intratumoral DNA methylation profiles will be generated to determine the degree of intratumoral DNA demethylation.
Assessment of disease response as a preliminary indication of efficacy of this combination against recurrent, refractory pediatric brain and solid tumors
Response to therapy, particularly in ependymoma will be evaluated to determine if a larger Phase II study is warranted.

Full Information

First Posted
June 21, 2017
Last Updated
September 23, 2021
Sponsor
The Hospital for Sick Children
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1. Study Identification

Unique Protocol Identification Number
NCT03206021
Brief Title
COZMOS:Phase I/Ib Trial of Combined 5'Azacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain/Solid Tumors
Acronym
COZMOS
Official Title
Phase I/Ib Trial of COmbined 5'aZacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain and Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 1, 2017 (Actual)
Primary Completion Date
July 1, 2022 (Anticipated)
Study Completion Date
July 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children

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
Many pediatric brain and solid tumors have altered epigenetic landscapes, and altered DNA methylation. As such this study is a Phase I/Ib study of combined 5'Azacitidine with an escalating dose of carboplatin for all recurrent/refractory pediatric brain and solid tumors. The phase I component will establish with maximum tolerated dose of carboplatin with azacytidine. An expansion cohort will be recruited of up to 30 patients will follow consisting of 20 recurrent posterior fossa ependymoma and 10 recurrent supratentorial ependymoma.
Detailed Description
Aberrant DNA methylation is frequently observed in many pediatric solid tumors, but in particularly several entities such as ependymoma, medulloblastoma, embryonal tumor with multilayered rosettes, atypical/teratoid rhabdoid tumor, neuroblastoma and wilm's tumor have promoter hypermethylation. Treatment with DNMTi (DNA methyltransferase inhibitors) agents such as 5-azacytidine has been shown to be safe and efficacious in adult myelodysplastic syndromes, causing significant decreased DNA methylation in blood, with maximum effect at day 15 of each cycle. However, monotherapy with DNMTi has been shown to result in resistance in leukamia's and efficacy in solid tumours is limited. Synergy between DNMTi and platinum agents has shown promise in pre-clinical models including pediatric ependymoma, and in addition, the combination of demethylating agents with carboplatin has provided promising results in platinum resistant ovarian cancers. However, this approach has not been applied to pediatric solid malignancies, which are attractive targets due to their frequent epigenetic dysregulation. Platinums are the backbone of therapy for most pediatric solid tumors, and as such it is an attractive hypothesis that part of the reason for resistance to upfront therapies is platinum resistance. Specifically, ependymoma's are highly chemoresistant tumors and studies in preclinical models of ependymoma support that this chemoresistance can be overcome with DNMTi. There is a clear medical need for new therapies, particularly for relapsed solid tumors, specifically brain tumors. Although pre-clinical data from our group and others suggests DNA demethylase inhibitors to be promising therapies for high risk ependymoma, medulloblastoma and ETMR (embryonal tumor with multilayered rosettes), 5'azacitidine monotherapy has been disappointing in clinical studies of adult solid tumours. Previous studies have suggested that platinum therapy can be effectively combined with azacitidine therapy and based on adult studies, maximum demethylation occurs approximately 5-10 days after treatment with 5'azacitidine. As such combination of azacitidine and carboplatin is a rationale therapy for several pediatric brain tumours, particularly those with a hypermethylated phenotype. Two phases of the study will be conducted. The Phase I will establish the maximum tolerated dose of carboplatin and 5'azacytidine in a rolling 6 design. 5'azacytidine will be administered on Days 1-7 followed by Carboplatin on Day 15. The initial dose level will be 5'Azacytidine 75mg/m2/day for 7 days with Carboplatin administered on Day 15 at AUC (Area under curve) 4. Carboplatin will be dose escalated to a maximum of AUC 6, or de-escalated to AUC 3. The Phase Ib will be an ependymoma specific expansion cohort at the established MTD (maximum tolerated dose), to determine the feasibility and initial efficacy of the combination of carboplatin and 5'azacytidine in patients with recurrent/refractory posterior fossa and supratentorial ependymoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Childhood CNS Tumor, Ependymoma, Recurrent Childhood, Childhood Solid Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase I Dose-escalation
Arm Type
Experimental
Arm Description
5'azacytidine will be administered on Days 1-7 at a dose of 75mg/m2/day, followed by escalating doses of Carboplatin on Day 14 in a rolling 6 design. Carboplatin will be dosed initially at AUC 4. Dose level -1 will reduce 5'azacytidine to 50mg/m2/day.
Arm Title
Posterior Fossa Ependymoma Expansion Arm
Arm Type
Experimental
Arm Description
5'azacytidine will be administered on days 1-7 and carboplatin will be administered on day 14 at the maximum tolerated dose achieved in the Phase I dose escalation to 20 patients with recurrent/refractory posterior fossa ependymoma.
Arm Title
Recurrent Brain and Solid Tumour Expansion Arm
Arm Type
Experimental
Arm Description
5'azacytidine will be administered on days 1-7 and carboplatin will be administered on day 14 at the maximum tolerated dose achieved in the Phase I dose escalation up to 12 patients with recurrent/refractory brain and solid tumour.
Intervention Type
Drug
Intervention Name(s)
5 Azacytidine
Other Intervention Name(s)
Carboplatin
Intervention Description
Dose escalation of carboplatin combined with 5'azacytidine
Primary Outcome Measure Information:
Title
Establish maximum tolerated dose of carboplatin in combination with 5'azacytidine
Description
Number of participants with treatment-related adverse events as assessed by the CTCAE4.0
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Characterization of the pharmacodynamics of 5'-azacitidine in combination with carboplatin
Description
Plasma pharmacodynamics will be assessed using methylation profiling of whole blood collected before and after administration of 5'Azacytidine, and after administration of carboplatin.
Time Frame
3 years
Title
Assessment of intratumoral DNA demethylation as a preliminary indication of biological efficacy of this combination.
Description
Where feasible, two cycles of 5'azacytidine and carboplatin will be administered prior to a biopsy and/or gross total resection, and intratumoral DNA methylation profiles will be generated to determine the degree of intratumoral DNA demethylation.
Time Frame
3 years
Title
Assessment of disease response as a preliminary indication of efficacy of this combination against recurrent, refractory pediatric brain and solid tumors
Description
Response to therapy, particularly in ependymoma will be evaluated to determine if a larger Phase II study is warranted.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Greater than the age of 1 year and under age 18 at the time of study enrolment Recurrent or refractory brain or solid tumor, including recurrent or refractory ependymoma Tissue from diagnosis or resection prior to registration must be available (either flash frozen tissue or an FFPE block) Previous therapy with carboplatin will be permitted Failed first line treatment (surgery, radiation therapy or chemotherapy) and should not be eligible for treatment with curative potential. Be at least 4 weeks from the completion of myelosuppressive chemotherapy and/or biologic agents before starting day 1 of this study treatment Be at least 14 days from the completion of radiation therapy and MIBG before starting day 1 of this study treatment Be at least 3 months post hematopoetic stem cell rescue following myeloablative therapy before starting day 1 of this study treatment Must have visible disease on imaging. Resection of visible disease is permitted while on study after two cycles including achievement of a gross total resection. If a resection is performed while on study, fresh frozen tissue should be submitted for analysis. Concurrent medications will be limited to supportive medications/agents including but not limited to anti-emetics, steroids, analgesics and non-enzyme inducing anticonvulsants. Strong inducers of the P450 system will not be permitted. Other concurrent medications require approval of the study Sponsor. Ability of the parent and/or child to understand and the willingness to sign a written informed consent document Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I for the Karnofsky-Lansky Scores). 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. Patients with posterior fossa syndrome/cerebellar mutism demonstrating clear improvement post-surgically can be enrolled based on physician discretion Adequate hepatic, renal, marrow and cardiac function as defined below within 28 days prior to cycle 1 day 1: Serum creatinine within normal institutional limits or creatinine clearance greater than 60mL/min Serum bilirubin <1.5 times upper limit of institutional normal. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis AST, ALT and Alkaline Phosphatase <3 times upper limit of institutional normal. If liver metastases are present, then <5 times upper limit of normal is permitted. Normal QTc interval at screening ECG (baseline echocardiogram is not required) Adequate marrow function defined below within 14 days prior to cycle 1 day 1: Leukocytes greater than or equal to 1000 x106/L Absolute neutrophil count greater than or equal to 0.75 x109/L Platelets greater than or equal to 75 x109/L Hemoglobin greater than or equal to 10g/dL (may be transfused). Exclusion Criteria: Female patient who is pregnant or breast feeding (Lactating females must agree not to breast feed while taking azacitidine) or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 6 months after the end of study treatment. Patients may not be receiving any other investigational agents within 30 days prior to day 1 of protocol treatment Prior therapy with a DNA demethylase inhibitor Evidence of cardiac toxicity (shortening fraction below 28%; shortening fraction measures and ratios the change in the diameter of the left ventricle between the contracted and relaxed states) Abnormal coagulation parameters (PT >15 seconds, PTT>40 seconds, and/or INR >1.5) Significant active cardiac disease within the previous 6 months including: NYHA class 3 or 4 CHF Unstable angina Myocardial infarction Known or suspected hypersensitivity to azacitidine or mannitol carboplatin Previous carboplatin exposure is not an exclusion criteria but previous allergic reaction to carboplatin will exclude enrolment. Patient must not require use of enzyme inducing anticonvulsants; patients who are receiving an enzyme inducing anticonvulsant must be able to switch to a non-enzyme inducing anticonvulsant such as Levetiracetam, Clobazam, Lacosamide, Valproate or Topiramate at least 2 weeks prior to study enrolment. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment) Active viral infection with HIV or hepatitis type B or C Patients with advanced malignant hepatic tumors Patients with advanced malignant hepatic tumors
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vijay Ramaswamy, MD PhD FRCPC
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Dirks, MD PhD FRCSC
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eric Bouffet, MD
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daniel Morgenstern, MD PhD
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Royal Children's Hospital Melbourne
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Women's and Children's Hospital
City
Adelaide
Country
Australia
Facility Name
Monash Children's Hospital
City
Clayton
Country
Australia
Facility Name
John Hunter Children's Hospital
City
Lambton
Country
Australia
Facility Name
Perth Children's Hospital
City
Perth
Country
Australia
Facility Name
Queensland Children's Hospital
City
South Brisbane
Country
Australia
Facility Name
Sydney Children's Hospital
City
Sydney
Country
Australia
Facility Name
Children's Hospital at Westmead
City
Westmead
Country
Australia
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
BC Children's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
McMaster Children's Hospital
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
Country
Canada
Facility Name
Children's Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X8
Country
Canada
Facility Name
Centre hospitalier universitaire Sainte-Justine
City
Montréal
State/Province
PQ
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montréal
State/Province
PQ
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24553142
Citation
Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stutz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jager N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, Taylor MD. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature. 2014 Feb 27;506(7489):445-50. doi: 10.1038/nature13108. Epub 2014 Feb 19.
Results Reference
result
PubMed Identifier
27269943
Citation
Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DT, Luu B, Cavalli FM, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FK, Santi M, van Veelen ML, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DP, Oba-Shinjo SM, Marie SK, Carlotti CG, Lee JY, Rao AA, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognar L, Klekner A, Hortobagyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, Chambless LB, Cain J, Eberhart CG, Ahsan S, Massimino M, Giangaspero F, Buttarelli FR, Packer RJ, Emery L, Yong WH, Soto H, Liau LM, Everson R, Grossbach A, Shalaby T, Grotzer M, Karajannis MA, Zagzag D, Wheeler H, von Hoff K, Alonso MM, Tunon T, Schuller U, Zitterbart K, Sterba J, Chan JA, Guzman M, Elbabaa SK, Colman H, Dhall G, Fisher PG, Fouladi M, Gajjar A, Goldman S, Hwang E, Kool M, Ladha H, Vera-Bolanos E, Wani K, Lieberman F, Mikkelsen T, Omuro AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW, Taylor MD. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. J Clin Oncol. 2016 Jul 20;34(21):2468-77. doi: 10.1200/JCO.2015.65.7825. Epub 2016 Jun 6.
Results Reference
result

Learn more about this trial

COZMOS:Phase I/Ib Trial of Combined 5'Azacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain/Solid Tumors

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