NL-OMON55442招募中2 期
INFORM2 exploratory multinational phase I/II combination study of Nivolumab and Entinostat in children and adolescents with refractory high-risk malignancies - INFORM2 NivEnt
Heidelberg University Hospital, Hopp Children's Cancer Center Heidelberg (KiTZ)0 个研究点目标入组 20 人开始时间: 待定最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 2 至 17（—）
入选标准
- •- Children and adolescents with refractory/relapsed/progressive high-risk CNS
- •tumors OR solid tumors OR with newly diagnosed high grade glioma. All specified
- •in the protocol.
- •- No standard of care treatment available
- •- Age at registration >= 2 to <= 21 years.
- •- Molecular analysis for biomarker identification (SNV load, high TILs or TLS
- •positive, MYC/N amplification) in laboratories complying with DIN EN ISO/IEC
- •17025 or similar via INFORM molecular diagnostic platform or equivalently valid
- •molecular pipeline
- •- Biomarker determined using whole exome sequencing (SNV load), IHC (high TILs
- •positive), whole genome- or whole exome sequencing (MYC/N amplification)
- •- In case molecular analysis was not performed via INFORM Registry molecular
- •pipeline: transfer of molecular data (whole exome and RNA sequencing)
- •- Time between biopsy/puncture/resection of the current
- •refractory/relapsed/progressive tumor and registration <= 24 weeks. In patients
- •receiving therapy not impacting biomarker stratification, time between
- •biopsy/puncture/resection of the current refractory/relapsed/progressive tumor
- •and registration of <= 36 weeks is allowed.
- •- Disease that is measurable as defined by RANO criteria or RECIST v1.1 (as
- •appropriate).
- •- Life expectancy > 3 months, Lansky >= 70 or Karnofsky >= 70.
- •-Laboratory requirements:
- •- Hematology: absolute granulocytes >= 1.0 × 10^9/l (unsupported)
- •platelets >= 100 × 10^9/l & stable
- •hemoglobin >= 8 g/dl or >= 4,96 nmol/L
- •- Biochemistry: Total bilirubin <= 1.5 x upper limit of normal (ULN)
- •AST(SGOT) <= 3.0 x ULN
- •ALT(SGPT) <= 3.0 x ULN
- •serum creatinine <= 1.5 x ULN for age
- •ECG: normal QTc interval according to Bazett formula <440ms
- •- Females of childbearing potential must have a negative serum or urine
- •pregnancy test within 7 days prior to initiation of treatment.
- •- Absence of any psychological, familial, sociological or geographical
- •condition potentially hampering compliance with the study protocol and
- •follow-up schedule; those conditions should be discussed with the patient
- •before registration in the trial
- •- Before patient screening and registration, written informed consent, also
- •concerning data and blood transfer, must be given
- •- No prior therapy with the combination of immune checkpoint inhibitors and
- •- Phase I: molecular analysis performed and biomarker status known (mutational
- •load, high TILs or TLS positive AND MYC(N) amplification status).
- •- Phase II: molecular analysis performed, biomarker status known (mutational
- •load, high TILs or TLS positive AND MYC(N) amplification status) and
- •stratification according to the following criteria:
- •- Group A: high mutational load (defined as > 100 somatic SNVs/exome) based on
- •whole exome sequencing
- •- Group B (enrolment closed): high PD-L1 mRNA expression (defined as reads per
- •million total reads per kilobase of exon model (RPKM) > 3) based on RNA
- •- Group C: Focal MYC(N) amplification based on whole exome sequencing or
- •ATRT-MYC subgroup
- 另有 4 项未显示
排除标准
- •-Patients with CNS tumors or metastases who are neurologically unstable despite
- •adequate treatment (e.g. convulsions).
- •- Patients with low-grade gliomas or tumors of unknown malignant potential are
- •not eligible
- •- Evidence of > Grade 1 recent CNS hemorrhage on the baseline MRI scan.
- •- Participants with bulky tumor on imaging are ineligible; bulky tumor are
- •defined in the protocol -
- •- Previous allogeneic bone marrow, stem cell or organ transplantation
- •- Diagnosis of immunodeficiency
- •- Diagnosis of prior or active autoimmune disease
- •- Evidence of interstitial lung disease
- •- Any contraindication to oral agents or significant nausea and vomiting,
- •malabsorption, or significant small bowel resection that, in the opinion of the
- •investigator, would preclude adequate absorption.
- •- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- •Known active hepatitis B or hepatitis C. Patients with past hepatitis B virus
- •(HBV) infection or resolved HBV infection are eligible. Patients positive for
- •hepatitis C antibody ar eliglible only if polymerase chain reaction is negative
- •form HCV RNA. see details in protocol
- •- Clinically significant, uncontrolled heart disease
- •- Major surgery within 21 days of the first dose. Gastrostomy,
- •ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and
- •insertion of central venous access devices are not considered major surgery,
- •but for these procedures, a 48 hour interval must be maintained before the
- •first dose of the investigational drug is administered.
- •- Any anticancer therapy within 2 weeks or at least 5 half-lives (whichever is
- •longer) of study drug administration.
- •- Confirmed radiotherapy induced pseudoprogression
- •- Traditional herbal medicines; these therapies are not fully studied and their
- •use may result in unanticipated drug-drug interactions that may cause or
- •confound the assessment of toxicity.
- •- History of hypersensitivity to the investigational medicinal product or to
- •any drug with similar chemical structure or to any excipient present in the
- •pharmaceutical form (including benzamide) of the investigational medicinal
- •- Participation in other ongoing clinical trials.
- •- Pregnant or lactating females.
- •- Presence of underlying medical condition that in the opinion of the
- •Investigator or Sponsor could adversely affect the ability of the subject to
- •comply with or tolerate study procedures and/or study therapy, or confound the
- •ability to interpret the tolerability of combned administration of entinostat
- •and nivolumab in treated subjects.
- •- Patients receiving systemic steroid therapy or any other form of
- •immunosuppressive therapy within 7 days prior to the first dose of study
- •treatment. The use of physiologic doses
- •of corticosteroids (up to 5 mg/m2/day prednisone equivalent) may be approved
- •after consultation with the Sponsor.
研究者
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