Actively Recruiting

Phase 1
Phase 2
Age: 2Years - 21Years
All Genders
NCT03838042

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

Led by University Hospital Heidelberg · Updated on 2024-02-07

91

Participants Needed

14

Research Sites

370 weeks

Total Duration

On this page

Sponsors

U

University Hospital Heidelberg

Lead Sponsor

G

German Cancer Research Center

Collaborating Sponsor

AI-Summary

What this Trial Is About

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).

CONDITIONS

Official Title

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

Who Can Participate

Age: 2Years - 21Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Children and adolescents aged 2 to 21 years with refractory, relapsed, or progressive high-risk CNS tumors or solid tumors
  • CNS tumors include medulloblastoma, ependymoma, ATRT, ETMR, pediatric high grade glioma (including DIPG), or other pediatric embryonal CNS tumors
  • Solid tumors include 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 tumors
  • Newly diagnosed high grade glioma in children and adolescents with constitutional mismatch repair deficiency syndrome after maximum safe surgical resection and no standard curative treatment option
  • No standard of care treatment available
  • Molecular analysis confirming biomarker status (high mutational load, MYC/N amplification, high TILs or TLS positive) performed in accredited laboratories
  • Time between biopsy/resection and registration ≤ 24 weeks (or ≤ 36 weeks if therapy does not impact biomarker stratification)
  • Measurable disease per RANO or RECIST v1.1 criteria
  • Life expectancy greater than 3 months and sufficient general condition score (Lansky or Karnofsky ≥ 70)
  • Hematology and biochemistry laboratory values within specified limits
  • Normal ECG QTc interval (< 440 ms)
  • Ability to swallow oral study medication
  • Ability of patient or legal representative to understand the trial and give informed consent
  • Negative pregnancy test for females of childbearing potential and agreement to use contraception
  • Absence of conditions hampering compliance with study procedures
  • No prior therapy with combination of immune checkpoint inhibitors and HDAC inhibitors
  • Molecular analysis and biomarker status known before Phase I and Phase II enrollment
  • Stratification into groups based on biomarker status for Phase II enrollment
Not Eligible

You will not qualify if you...

  • Neurologically unstable patients with CNS tumors or metastases despite treatment
  • Patients with low-grade gliomas or tumors of unknown malignant potential
  • Recent CNS hemorrhage greater than Grade 1 on baseline MRI
  • Bulky CNS tumors with uncal herniation, severe midline shift, diameter >6 cm, or significant mass effect
  • Previous allogeneic bone marrow, stem cell, or organ transplantation
  • Diagnosis of immunodeficiency or prior/active autoimmune disease
  • Evidence of interstitial lung disease
  • Contraindications to oral agents or conditions affecting drug absorption
  • Known HIV infection or active hepatitis B or C virus infection
  • Clinically significant uncontrolled heart disease
  • Major surgery within 21 days before first dose (except specific minor procedures with 48-hour interval)
  • Recent anticancer therapy within 2 weeks or at least 5 half-lives before study drug administration
  • Radiotherapy-induced pseudoprogression in CNS tumors
  • Use of traditional herbal medicines that could interfere with study drugs
  • History of hypersensitivity to investigational product or similar drugs
  • Participation in other ongoing clinical trials
  • Pregnant or lactating females
  • Underlying medical conditions that could affect compliance or interpretation of treatment effects
  • Systemic steroid or immunosuppressive therapy within 7 days prior to first dose (physiologic corticosteroids may be allowed after consultation)
  • Previous enrollment in this trial

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

1
2
3
+1

Trial Site Locations

Total: 14 locations

1

Sydney Children's Hospital

Randwick, New South Wales, Australia, 2031

Actively Recruiting

2

Children's Hospital at Westmead

Westmead, New South Wales, Australia, 2145

Actively Recruiting

3

Royal Children's Hospital

Parkville, Victoria, Australia, 3052

Actively Recruiting

4

Perth Children's Hospital

Nedlands, Western Australia, Australia, 6009

Actively Recruiting

5

St. Anna Children's Hospital

Vienna, Austria, 1090

Actively Recruiting

6

Institut Curie

Paris, France, 75005

Actively Recruiting

7

Augsburg University Hospital

Augsburg, Germany, 86156

Actively Recruiting

8

Charité University Medicine Berlin

Berlin, Germany

Actively Recruiting

9

Essen University Hospital

Essen, Germany

Actively Recruiting

10

Hannover Medical School

Hanover, Germany

Actively Recruiting

11

Hopp Children's Cancer Center Heidelberg (KiTZ)

Heidelberg, Germany, 69120

Actively Recruiting

12

Prinses Máxima Centrum

Utrecht, Netherlands

Actively Recruiting

13

Karolinska Institute

Stockholm, Sweden

Actively Recruiting

14

Children's Hospital Zurich

Zurich, Switzerland, 8032

Actively Recruiting

Loading map...

Research Team

V

Venukah Schäfer

CONTACT

M

Melanie Heiß

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

Not the Right Trial for You?

Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.

Already have an account? Log in here