IRB Study Number 17-1060
Status Recruiting
Phase Phase 2
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary Aims
1 To utilize clinical and biological data to screen for eligibility to phase 2 pathway-targeting specific subprotocols of pathway-targeting agents in pediatric patients with advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
2 To determine the proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs.
3 To determine the objective response rates (ORR; complete response + partial response) in pediatric patients with advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders harboring a priori specified genomic alterations treated with pathway-targeting agents.
Secondary Aims
1 To estimate the progression free survival in pediatric patients receiving targeted therapies for advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
2 To obtain preliminary or additional information about the tolerability of targeted therapies in children with advanced cancers.
3 To provide preliminary estimates of the pharmacokinetics of targeted therapies in children with advanced cancers.
4 To obtain preliminary information on the response rate to targeted therapy in patients whose tumors lack actionable alterations as defined for the MATCH study, for selected agents for which efficacy is observed in the primary matched cohort.
Exploratory Aims
1 To increase knowledge of the genomic landscape of advanced pediatric solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
2 To describe the genomic changes that occur in advanced pediatric cancers between the time of initial diagnosis and relapse, in cases for which paired tumor specimens are available.
3 To explore approaches to diagnosing and profiling genomics of advanced pediatric cancers through evaluation of circulating tumor DNA
4 To determine the frequency and spectrum of germline cancer susceptibility mutations in children with relapsed solid tumors and non-Hodgkin lymphomas and assess the feasibility of return of those results in the NCTN group setting.
Inclusion Criteria
1 Age: Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment.
2 Diagnosis: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. LCH, JXG, histiocytic sarcoma), and CNS tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG. In cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence. Please Note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible.
3 Tumor Sample Availability: Patients must have an FFPE tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians including but not limited to the procedures listed in Section 5.2 below. A tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process.
4 Performance Status: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age). Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. 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.
5 Disease Status: Patients must have radiographically measurable disease (Refer to Section 12). Measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment. Patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on MRI and visible on more than one slice.
Note: The following do not qualify as measurable disease:
malignant fluid collections (e.g., ascites, pleural effusions)
bone marrow infiltration except that detected by MIBG scan for neuroblastoma
lesions only detected by nuclear medicine studies (e.g., bone, gallium or PET scans) except as noted for neuroblastoma
elevated tumor markers in plasma or CSF
previously radiated lesions that have not demonstrated clear progression post radiation
leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1.
General Inclusion Criteria for Subprotocols - NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 8 weeks (56 days) of treatment assignment.
1 Performance Status: (See Section 4)
2 Disease Status: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease. (See Section 12). Patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible. Measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on MRI and visible on more than one slice.
Note: The following do not qualify as measurable disease:
malignant fluid collections (e.g., ascites, pleural effusions)
bone marrow infiltration except that detected by MIBG scan for neuroblastoma
lesions only detected by nuclear medicine studies (e.g., bone, gallium or PET scans) except as noted for neuroblastoma
elevated tumor markers in plasma or CSF
previously radiated lesions that have not demonstrated clear progression post radiation
leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1.
3 Prior Therapy: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
3.1 Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately.
a. Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive.
See https://www.cogmembers.org/site/disc/devtherapeutics/default.aspx for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.≥ 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
b. Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent.
See https://www.cogmembers.org/site/disc/devtherapeutics/default.aspx for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
c. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
d. Corticosteroids: If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid.
e. Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator.
f. Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors)
g. Stem cell Infusions (with or without TBI):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: ≥ 84 days after infusion and no evidence of GVHD.
• Autologous stem cell infusion including boost infusion: ≥ 42 days.
h. Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
i. XRT/External Beam Irradiation including Protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial BM radiation. Note: Radiation may not be delivered to “measurable disease” tumor site(s) being used to follow response to subprotocol treatment.
j. Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): ≥ 42 days after systemically administered radiopharmaceutical therapy.
4 Organ Function Requirements: (See protocol)
5 Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned.
6 Agent specific limitations on prior therapy will be included with specific treatment subprotocols.
Exclusion Criteria
General Exclusion Criteria for Subprotocols
1 Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in females who are post-menarcheal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
2 Concomitant Medications:
2.1 Corticosteroids: At the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid.
2.2 Investigational Drugs: Patients must meet criteria for prior therapy (Section 3) at the time of consent and enrollment to a subprotocol. Other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol (See Section 8).
2.3 Anticancer Agents: Patients must meet criteria for prior therapy (Section 3) at the time of consent and enrollment to a subprotocol. Other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol (See Section 8).
2.4 Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible.
3 Infection: Patients who have an uncontrolled infection are not eligible.
4 Patients who have had a prior solid organ transplant are not eligible.
5 Additional agent specific criteria will be included with specific treatment subprotocols.
