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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04195555




Registration number
NCT04195555
Ethics application status
Date submitted
11/12/2019
Date registered
12/12/2019

Titles & IDs
Public title
Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
Scientific title
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of AG-120 (Ivosidenib) in Patients With Tumors Harboring IDH1 Mutations
Secondary ID [1] 0 0
NCI-2019-08098
Secondary ID [2] 0 0
NCI-2019-08098
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Ependymoma 0 0
Recurrent Ewing Sarcoma 0 0
Recurrent Hepatoblastoma 0 0
Recurrent Langerhans Cell Histiocytosis 0 0
Recurrent Malignant Germ Cell Tumor 0 0
Recurrent Malignant Glioma 0 0
Recurrent Malignant Solid Neoplasm 0 0
Recurrent Medulloblastoma 0 0
Recurrent Neuroblastoma 0 0
Recurrent Non-Hodgkin Lymphoma 0 0
Recurrent Osteosarcoma 0 0
Recurrent Peripheral Primitive Neuroectodermal Tumor 0 0
Recurrent Rhabdoid Tumor 0 0
Recurrent Rhabdomyosarcoma 0 0
Recurrent Soft Tissue Sarcoma 0 0
Recurrent WHO Grade 2 Glioma 0 0
Refractory Ependymoma 0 0
Refractory Ewing Sarcoma 0 0
Refractory Hepatoblastoma 0 0
Refractory Langerhans Cell Histiocytosis 0 0
Refractory Malignant Germ Cell Tumor 0 0
Refractory Malignant Glioma 0 0
Refractory Malignant Solid Neoplasm 0 0
Refractory Medulloblastoma 0 0
Refractory Neuroblastoma 0 0
Refractory Non-Hodgkin Lymphoma 0 0
Refractory Osteosarcoma 0 0
Refractory Peripheral Primitive Neuroectodermal Tumor 0 0
Refractory Rhabdoid Tumor 0 0
Refractory Rhabdomyosarcoma 0 0
Refractory Soft Tissue Sarcoma 0 0
Refractory WHO Grade 2 Glioma 0 0
Wilms Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ivosidenib

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.


Treatment: Drugs: Ivosidenib
Given PO
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response rate (ORR; complete response + partial response) in pediatric patients treated with ivosidenib
Timepoint [1] 0 0
From enrollment to the end of treatment, up to 2 years
Secondary outcome [1] 0 0
Progression free survival (PFS)
Timepoint [1] 0 0
From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 5 years
Secondary outcome [2] 0 0
Percentage of patients experiencing grade 3 or higher adverse events
Timepoint [2] 0 0
From enrollment to the end of treatment, up to 2 years
Secondary outcome [3] 0 0
Preliminary estimates of the pharmacokinetics (PK) of ivosidenib in children and adolescents with relapsed or refractory cancer
Timepoint [3] 0 0
Pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 1; pre-dose on cycle 1, day 2; pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 15; and pre-dose on cycle 2, day 1 and cycle 4, day 1
Secondary outcome [4] 0 0
Preliminary estimates of the pharmacodynamics (PD) of ivosidenib in children and adolescents with relapsed or refractory cancer
Timepoint [4] 0 0
Pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 1; pre-dose on cycle 1, day 2; pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 15; and pre-dose on cycle 2, day 1 and cycle 4, day 1

Eligibility
Key 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 as defined in APEC1621SC
* Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment
* Patients must have a body surface area >= 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 any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)

* 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 =< 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 score.
* 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. >= 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 =< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 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 1.5, female 1.4
* Age >= 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]) =< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior to enrollment)
* Serum albumin >= 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 =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* 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 guidelines
Minimum age
12 Months
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or breast-feeding women will not be entered on this study due to risks because there is yet no available information regarding human fetal or teratogenic toxicities. 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 non-hormonal contraceptive method for the duration of study treatment and for at least 1 month after last dose of AG-120 (ivosidenib). Since AG-120 (ivosidenib) may decrease concentrations of hormonal contraceptives, hormonal contraceptives are not considered effective contraception when co-administered with AG-120 (ivosidenib)
* 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, >= 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
49
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Alabama
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United States of America
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Alaska
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Georgia
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Illinois
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North Carolina
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Ohio
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Utah
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Vermont
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Washington
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West Virginia
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Wisconsin
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Puerto Rico
State/province [48] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Oncology Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Elizabeth D Alva
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://grants.nih.gov/policy/sharing.htm


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04195555