Recruiting PHASE1, PHASE2 CNS Tumor

New treatment option for CNS Tumor

Official title INFORM2 Study Uses Nivolumab and Entinostat in Children and Adolescents With High-risk Refractory Malignancies

ClinicalTrials.gov ID: NCT03838042

What this study is testing

What is Nivolumab and Entinostat?

Nivolumab and Entinostat is an investigational medicine, being studied as a potential treatment for cns tumor.

Also referred to as Opdivo.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: The aim of this trial is to determine preliminary activity of the combination treatment with nivolumab and entinostat in children and adolescents with high risk refractory/relapsed/progressive tumors harboring a high mutational load, focal MYC(N) amplification or ATRT-MYC subgroup as well as tumors with high tumor infiltrating lymphocytes (TILs) or a tertiary lymphoid structure (TLS).

Phase 2: a mid-size study of how well it works

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 2 to 21

You may be able to join if

Children and adolescents with refractory/relapsed/progressive high-risk
CNS tumors: medulloblastoma, ependymoma, ATRT, ETMR, pediatric high grade glioma (including DIPG) or other pediatric embryonal CNS tumors OR
solid tumors: neuroblastoma, nephroblastoma, rhabdoid tumor, embryonal or alveolar rhabdomyosarcoma, other embryonal small round blue cell tumors...
Children and adolescents with newly diagnosed high grade glioma (HGG) in the context of a constitutional mismatch repair deficiency syndrome after...
No standard of care treatment available

You likely can't join if

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 CNS tumor on imaging are ineligible; bulky tumor is defined as:
Tumor with any evidence of uncal herniation or severe midline shift
Tumor with diameter of \> 6 cm in one dimension on contrast-enhanced MRI

See the full eligibility criteria

Who can join

Children and adolescents with refractory/relapsed/progressive high-risk
CNS tumors: medulloblastoma, ependymoma, ATRT, ETMR, pediatric high grade glioma (including DIPG) or other pediatric embryonal CNS tumors OR
solid tumors: neuroblastoma, nephroblastoma, rhabdoid tumor, embryonal or alveolar rhabdomyosarcoma, other embryonal small round blue cell tumors including pediatric type (bone) sarcoma or other pediatric type solid...
Children and adolescents with newly diagnosed high grade glioma (HGG) in the context of a constitutional mismatch repair deficiency syndrome after maximum safe surgical resection with no established standard of care...
No standard of care treatment available
Age at registration ≥ 2 to ≤ 21 years
Molecular analysis for biomarker identification (SNV load, MYC/N amplification, high TILs or TLS positive) in laboratories complying with DIN EN ISO/IEC 17025 or similar via INFORM molecular diagnostic platform or...
Biomarker determined using whole exome sequencing (SNV load), whole genome- or whole exome sequencing (MYC/N amplification), IHC (high TILs or TLS positive)
In case molecular analysis was not performed via INFORM Registry molecular pipeline: transfer of molecular data (whole exome 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...
Disease that is measurable as defined by RANO criteria or RECIST v1.1 (as appropriate).
Life expectancy \> 3 months, sufficient general condition score (Lansky ≥ 70 or Karnofsky ≥ 70). Transient states like infections requiring antibiotic treatments can be accepted, and also stable disabilities resulting...
Laboratory requirements:
Hematology:
absolute granulocytes ≥ 1.0 × 109/l (unsupported)
platelets ≥ 100 × 109/l \& stable
hemoglobin ≥ 8 g/dl or ≥ 4.96 mmol/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
Patient is able to swallow oral study medication
Ability of patient and/or legal representative(s) to understand the character and individual consequences of clinical trial
Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active women of childbearing potential must agree to use acceptable and...
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 patient screening and registration, written informed consent, also concerning data and blood transfer, must be given according to ICH/GCP, and national/local regulations.
No prior therapy with the combination of immune checkpoint inhibitors and HDACi
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 OR
Group C: Focal MYC(N) amplification based on whole genome sequencing or whole exome sequencing ot ATRT-MYC subgroup OR
Group E: high TILs or TLS positive (defined as cells per mm² \> 600 or presence of tertiary lymphoid structure) based on IHC analysis.

What rules you out

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 CNS tumor on imaging are ineligible; bulky tumor is defined as:
Tumor with any evidence of uncal herniation or severe midline shift
Tumor with diameter of \> 6 cm in one dimension on contrast-enhanced MRI
Tumor that in the opinion of the investigator, shows significant mass effect
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 (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative])...
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...
Any anticancer therapy (e.g., chemotherapy, HDACi (including valproic acid), DNA methyltransferase inhibitors, other immunotherapy, targeted therapy, biological response modifiers, endocrine anticancer therapy or...
Radiologically confirmed radiotherapy induced pseudoprogression in CNS tumors
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. As part of the...
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...
Participation in other ongoing clinical trials.
Pregnant or lactating females.
Presence of underlying medical condition (e.g. gastrointestinal disorders or electrolyte disturbances) that in the opinion of the Investigator or Sponsor could adversely affect the ability of the subject to comply with...
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...

The study team makes the final eligibility decision.

Where it's taking place

Randwick, New South Wales, Australia
Westmead, New South Wales, Australia
Parkville, Victoria, Australia
Nedlands, Western Australia, Australia
Vienna, Austria
Paris, France
Augsburg, Germany
Berlin, Germany
Essen, Germany
Hanover, Germany
Heidelberg, Germany
Utrecht, Netherlands
Stockholm, Sweden
Zurich, Switzerland

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 2 years to 21 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Randwick, New South Wales, Australia; Westmead, New South Wales, Australia; Parkville, Victoria, Australia; Nedlands, Western Australia, Australia; Vienna, Austria; Paris, France and 8 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.