APEC1621I: NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 subprotocol of Palbociclib in Patients with Tumors Harboring Activating Alterations in Cell Cycle Genes
Johns Hopkins Kimmel Cancer Center in Baltimore
This phase II Pediatric MATCH trial studies how well palbociclib works in treating patients with Rb positive solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations (mutations) in cell cycle genes that have spread to other places in the body and have come back or do not respond to treatment. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria:1. Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621I based on the presence of an actionable mutation*Positive Rb expression by immunohistochemistry is required for study enrollment3. Patients must have a body surface area greater than equal to 0.87 m^2 at enrollment4. Patients must have radiographically measurable disease at the time of study 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 magnetic resonance imaging (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 positron emission tomography [PET] scans) except as noted for neuroblastoma*Elevated tumor markers in plasma or cerebrospinal fluid (CSF)*Previously radiated lesions that have not demonstrated clear progression post radiation*Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.15. Karnofsky greater than equal to 50% for patients greater than 16 years of age and Lansky greater than equal to 50 for patients equal to less than 16 years of age; Note: Neurologic deficits in patients with CNS tumors must have been relatively 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 score6. Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately*Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive* greater than equal to 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)*Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC] counts): greater than equal to 7 days after the last dose of agent*Antibodies: greater than equal to 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade equal to less than 1*Corticosteroids: If used to modify immune adverse events related to prior therapy, greater than equal to 14 days must have elapsed since last dose of corticosteroid*Hematopoietic growth factors: greater than equal to 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors 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*Interleukins, interferons and cytokines (other than hematopoietic growth factors): greater than equal to 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)*Stem cell infusions (with or without total body irradiation [TBI]):*Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: greater than equal to 84 days after infusion and no evidence of graft versus host disease (GVHD)*Autologous stem cell infusion including boost infusion: greater than equal to 42 days*Cellular therapy: greater than equal to 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)*Radiation therapy (XRT)/external beam irradiation including protons: greater than equal to 14 days after local XRT; greater than equal to 150 days after TBI, craniospinal XRT or if radiation to greater than equal to 50% of the pelvis; greater than equal to 42 days if other substantial bone morrow (BM) radiation*Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment*Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): greater than equal to 42 days after systemically administered radiopharmaceutical therapy*Patients must not have received prior exposure to palbociclib, ribociclib, abemaciclib or any other CDK4/6 inhibitors7. For patients with solid tumors without known bone marrow involvement:*Peripheral absolute neutrophil count (ANC) greater than equal to 1000/mm^3*Platelet count greater than equal to 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)8. Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity9. Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater than equal to 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:*Age: 1 to less than 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6*Age: 2 to less than 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8*Age: 6 to less than 10 years; maximum serum creatinine (mg/dL): male 1; female 1*Age: 10 to less than 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2*Age: 13 to less than 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4*Age: greater than equal to 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.410. Bilirubin (sum of conjugated + unconjugated) equal to less than 1.5 x upper limit of normal (ULN) for age11. Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) equal to less than 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)12. Serum albumin greater than equal to 2 g/dL13. Patients must be able to swallow intact capsules14. 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 guidelinesExclusion Criteria:1. Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment; female study participants of child-bearing potential and their partners, should agree to use highly effective forms of contraception for at least 3 weeks after the last dose of palbociclib; male study participants should avoid fathering a child, donating sperm, and should agree to use highly effective forms of contraception for at least 3 months after the last dose of palbociclib2. Concomitant medications*Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, greater than equal to 14 days must have elapsed since last dose of corticosteroid*Investigational drugs: Patients who are curren
Patients receive palbociclib by mouth once a day on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
01/19/2020 05:03 AM