|Protocol||Trial Name and Objective|
A first-in-human phase I single-agent open-label dose-escalation study of every three-week dosing of oral ONC201 in patients with advanced solid tumors
To determine the recommended maximal tolerated dose (MTD) or recommended phase II dose of single agent ONC201 orally once every three weeks
To characterize the safety and tolerability of ONC201 in patients with tumors that have a high frequency of PI3 kinase pathway or RAS signaling activation (metastatic castrate resistant prostate cancer, metastatic renal cell carcinoma, melanoma, glioblastoma multiforme, breast cancer).
COG-ACNS0332: Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients
1. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/PNET patients.
2. To determine whether Isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients.
3. To compare residual disease response to radiation alone versus radiation plus carboplatin.
4. To identify molecular prognostic indicators suitable for patient stratification in future trials.
5. To evaluate the HRQOL during phases of active treatment specific to treatment modalities.
6. To describe the neuropsychological functioning of the study population and to evaluate the relationship
between neuropsychological status and health related quality of life.
COG ACNS0831: Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients with Newly Diagnosed Ependymoma Ages 1 to 21 years
1. To determine the event free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with post-operative conformal radiation therapy (cRT) and then randomized to receive or not receive four cycles of post radiation maintenance chemotherapy with vincristine, cisplatin, etoposide and cyclophosphamide (VCEC).
2. To estimate the EFS and OS of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by a) post-operative induction chemotherapy or by b) second surgery who will then be non-randomly assigned to cRT followed by four cycles of maintenance chemotherapy (VCEC)
3. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short course induction chemotherapy following first surgery.
COG ACNS1022: A Phase II Randomized Trial of Lenalidomide (NSC # 703813, IND # 70116) in Pediatric Patients with Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas
1. To determine the objective response rate of children with recurrent, refractory or progressive juvenile astrocytomas and optic pathway gliomas who are treated with low-dose (20 mg/m2/dose) or high dose (115 mg/m2/dose) lenalidomide.
2. To estimate the event free survival of these patients when treated with lenalidomide
3. To correlate pharmacokinetics with objective response
4. To evaluate toxicities of long term lenalinomide use
RTOG 1205: Randomized Phase II Trial of Concurrent Bevacizumab and Re-Irradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma
To establish an improvement in overall survival in recurrent GBM patients receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone.
Secondary objectives include:
To estimate and compare the rate of objective response in patients with measurable disease.
To estimate and compare the 6-month progression-free survival rate.
To estimate and compare progression-free survival.
To estimate and compare the rate of treatment adverse events.
To estimate and compare the rate of ?grade 3 acute or delayed CNS toxicity.
COG ACNS1123: Phase 2 Trial of Response-Based Radiation Therapy for Patients with Localized Central Nervous System Germ Cell Tumors (CNS GCT)
1. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults (ages 3 to Ü 21 years) with localized non-
germinomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.
2. To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults (ages 3 to Ü 21 years) with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCG Â) Ü50 mIU/ml
3. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (Germinoma) using the ALTE07C1 protocol. This objective will be assessed independently for the two strata.
4. To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6Gy WVI and involved field focal (IFR) boost to 54Gy.
5.To estimate the PFS and OS distributions of
localized germinoma patients who present with
a) serum and/or CSF hCGÂ Ü50mIU/ml and b) serum and/or CSF hCG
Â> 50mIU/ml and Ü100mIU/ml.
N0577: Phase III Intergroup Study of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deleted Anaplastic Glioma
To determine whether patients who receive radiotherapy with concomitant temozolomide followed by adjuvant temozolomide have a marginally better p rogression free survival (PFS) than patients who receive radiotherapy followed by PCV chemotherapy.
To determine whether patients who receive temozolomide (TMZ) alone have a
significantly longer time to progression (neurocognitive, clinical or radiographic progression) than patients who receive radiotherapy with concomitant TMZ followed by adjuvant TMZ or radiotherapy followed by PCV chemotherapy
COG ACNS1221: A Phase II Study for the Treatment of Non-Metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age
1. Estimate of the PFS distribution for patients 0-<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).
2.Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.
3.Prospectively evaluate the molecular profile of ND/MBEN medulloblastoma in young children.
4. Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.
COG-ACNS0821 - Temozolomide with Irinotecan versus Temozolomide, Irinotecan plus Bevacizumab for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, A COG Randomized Phase II Screening Trial
1.To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan and bevacizumab for recurrent medulloblastoma (MB)/PNET of childhood.
2.To assess the response rate for each treatment arm amongst patients who are enrolled with measurable disease.
3. To determine event-free survival (EFS) for each patient compared across regimens.
NRG-BN001: Randomized, Phase II Trial of Hypofractionated Dose-escalated Photon IMRT or Proton Beam Therapy versus Conventional Photon Irradiation with Concomitant and Adjuvant Temozolomide in Patients with Newly Diagnosed Glioblastoma.
To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves overall survival, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.
2.2.1 To indirectly compare dose-escalated and -intensified photon IMRT to dose-escalated and -intensified proton beam therapy in terms of overall survival.
2.2.2 To indirectly compare and record toxicities of dose-escalated and -intensified photon IMRT versus dose-escalated and -intensified proton beam therapy and directly compare the toxicities of these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide
2.2.3 To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.
2.2.4 To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide.
2.2.5 To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to dose-escalated and -intensified photon IMRT, and to directly compare symptom burden with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide
2.2.6 To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to dose-escalated and -intensified photon IMRT, and to directly compare neurocognitive function with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide
2.3.1 Tissue banking for future translational science projects that will be determined based on the state of the science at the time the primary endpoint is reported and will be submitted to NCI for review and approval.
2.3.2 To prospectively compare CD4 lymphopenia between dose-escalated and intensified proton beam therapy, dose-escalated and -intensified photon IMRT, and standard-dose photon irradiation and determine whether CD4 lymphopenia impacts overall survival.
2.3.3 To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout radiation therapy processes, including imaging, simulation, patient immobilization, target and critical structure definition, treatment planning, image guidance and delivery.
X To establish feasibility anand clinical relevancy of quality assurance guidelines
X To evaluate efficacy of quality assurance tools
2.3.4 To explore the most appropriate and clinically relevant advanced and standard MRI imaging parameters
X To evaluate the feasibility of differentiating pseudo-progression and true progression in a multi institutional setting using MR diffusion and perfusion imaging.
X To evaluate for early, imaging biomarkers of response and overall survival.
A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects with Melanoma Metastatic to the Brain treated with Nivolumab in Combination with Ipilimumab followed by Nivolumab Monotherapy
Primary Objective: To assess the CNS clinical benefit rate (CBR, defined as CR + PR + SD > 6 months per protocol-defined response criteria) in subjects with malignant melanoma metastatic to the brain treated with nivolumab combined with ipilimumab followed by nivolumab monotherapy.