Protocol Summary

Protocol No.: OCR37342

Sponsor Protocol No.: APEC1621K

Protocol Title.: Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)

Principal Investigator: Slayton, William

Objective: This phase II Pediatric MATCH trial studies how well ivosidenib works in treating patients with solid tumors that have spread to other places in the body (advanced), lymphoma, or histiocytic disorders that have IDH1 genetic alterations (mutations). Ivosidenib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway called the IDH pathway.

Description: PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with AG-120 (ivosidenib) with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the IDH1 pathway. SECONDARY OBJECTIVES: I. To estimate the progression free survival in pediatric patients treated with AG-120 (ivosidenib) with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the IDH1 pathway. II. To obtain information about the tolerability of AG-120 (ivosidenib) in children and adolescents with relapsed or refractory cancer. III. To provide preliminary estimates of the pharmacokinetics and pharmacodynamics of AG-120 (ivosidenib) in children and adolescents with relapsed or refractory cancer. EXPLORATORY OBJECTIVES: I. To evaluate other biomarkers as predictors of response to AG-120 (ivosidenib) and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to AG-120 (ivosidenib) treatment. II. To explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA). OUTLINE: Patients receive ivosidenib orally (PO) once daily (QD). Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Phase: Phase II

Age Group: Both

Age: 12 Months - 21 Years

Gender: All

Scope: National

Treatment:

Experimental: Treatment (ivosidenib)
Patients receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Detailed Eligibility:

Inclusion Criteria: - Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621K based on the presence of an actionable mutation - Patients must be >= than 12 months and == 0.78 m^2 at enrollment - Patients must be able to swallow intact tablets - Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (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) 1.1. - Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients == 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 count [ANC] counts): >= 7 days after the last dose of agent - 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 == 14 days must have elapsed since last dose of corticosteroid - Hematopoietic growth factors: >= 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): >= 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: >= 84 days after infusion and no evidence of graft versus host disease (GVHD) - Autologous stem cell infusion including boost infusion: >= 42 days - Cellular Therapy: >= 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: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (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): >= 42 days after systemically administered radiopharmaceutical therapy - Patients must not have received prior exposure to AG-120 (ivosidenib) or other IDH1 inhibitors - For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment) - For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) - Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood count (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 toxicity - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment), or - A serum creatinine based on age/gender (within 7 days prior to enrollment) - Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6 - Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8 - Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1 - Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2 - Age 13 to = 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4 - Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) - Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) == 2 g/dL (within 7 days prior to enrollment) - Corrected QT (QTc )interval =< 450 milliseconds (within 7 days prior to enrollment) - Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades de Pointes. Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available - Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled - Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) resulting from prior therapy must be == 14 days must have elapsed since last dose of corticosteroid - Patients who are currently receiving another investigational drug are not eligible - Patients who are currently receiving other anti-cancer agents are not eligible - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial - Patients who are currently receiving drugs that are strong inducers or moderate to strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to strong inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed. In addition, patients receiving sensitive or narrow therapeutic range substrates of CYP3A4 are not eligible - Patients with a history of progressive multifocal leukoencephalopathy are not eligible - Patients who have an uncontrolled infection are not eligible - Patients who have received a prior solid organ transplantation 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

Applicable Conditions:

  • Brain and Nervous System
  • Gastrointestinal Cancer
  • Kidney Cancer (Renal Cell)
  • Lung Cancer
  • Lymphoma - Non-Hodgkin
  • Ovarian Cancer
  • Pediatric (Childhood) Cancer
  • Sarcoma
  • Participation Institution:

  • UF Gainesville : Heather Rogers
  • Contact:
    Heather Rogers
    Phone: +1 352-294-8743
    Email: heatherrogers@ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT04195555