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Fimepinostat in Treating Younger Patients with Relapsed or Refractory Solid Tumors, Central Nervous System Tumors, or Lymphoma

Trial Status: Active

This phase I trial studies the side effects of fimepinostat in treating younger patients with solid tumors, central nervous system tumors, or lymphoma that has come back or does not respond to treatment. Fimepinostat may stop the growth of cancer or tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • Karnofsky performance status >= 50% for patients >= 16 years of age and Lansky >= 50% for patients < 16 years of age
  • For Parts A and B, participants must have evaluable or measurable disease
  • For Part A, participants must have histologically confirmed solid tumors, CNS tumors, or lymphoma based upon biopsy or surgery at initial diagnosis and/or relapse/progression; the only exception to histologic confirmation is for pediatric tumors that are routinely diagnosed exclusively by standard clinical imaging criteria: diffuse intrinsic pontine glioma and optic pathway glioma
  • For Part B, participants must have one of the following diagnoses histologically confirmed: * Neuroblastoma with evidence of mycn/myc positivity based on any of the following: ** MYCN amplification (> 4 copy amplification) from Children's Oncology Group (COG) reference laboratory or other Clinical Laboratory Improvement Act (CLIA)-certified laboratory; or ** Mycn protein expression >= 1+ according to validated assay in Children’s Hospital Los Angeles (CHLA) Clinical Pathology Laboratory; or ** Myc expression >= 1+ according to validated assay in CHLA Clinical Pathology Laboratory * One of the following mature B cell lymphoma diagnoses: ** Diffuse large B cell lymphoma ** Burkitt lymphoma * An extra-cranial, solid tumor, other than neuroblastoma, with evidence of MYC or MYCN-alteration based on either of the following: ** MYC or MYCN amplification from a CLIA-certified laboratory ** MYC or MYCN high copy gain from a CLIA-certified laboratory
  • Participants must have disease that is relapsed or refractory and for which standard curative or palliative measures do not exist or are no longer effective
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy except organ function; patients must meet the following minimum washout periods prior to enrollment: * At least 14 days after the last dose of myelosuppressive chemotherapy (42 days for nitrosourea or mitomycin C) * Radiotherapy: ** At least 14 days after local palliative radiation therapy (XRT) (small port); ** At least 90 days must have elapsed after prior total body irradiation (TBI), craniospinal XRT or if > 50% radiation of pelvis; ** At least 42 must have elapsed if other substantial bone marrow (BM) radiation; ** At least 42 days must have passed since last iobenguane (MIBG) or other radionuclide therapy * At least 7 days following the last dose of a biologic agent; for agents with known adverse events occurring beyond 7 days, this duration must be extended beyond the time in which adverse events are known to occur; if extended duration is required, this should be discussed and approved by the study chair * Monoclonal antibody: At least 21 days must have elapsed after the last dose of antibody * At least 14 days following the last dose of long-acting growth factor (e.g. Neulasta) or 7 days following short-acting growth factor * The patient must have no evidence of graft versus host disease and at least 42 days must have elapsed after transplant, stem cell infusion, or cellular therapy * At least 3 weeks from prior major surgical procedure; Note: Biopsy and central line placement/removal are not considered major * The patient must not have received prior CUDC-907 therapy; prior treatment with individual PI3K or HDAC inhibitors is allowed; patients must not have received therapy with the combination of PI3K and HDAC inhibitors
  • Absolute neutrophil count >= 1,000/uL
  • Platelets >= 75,000/uL and transfusion independent, defined as not receiving a platelet transfusion for at least 5 days prior to complete blood count (CBC) documenting eligibility
  • Total bilirubin =< 1.5 x upper limit of normal for age
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 135 U/L; for the purpose of this study, the upper limit of normal (ULN) for ALT is 45 U/L
  • Serum albumin >= 2 g/dL
  • A serum creatinine based on age/gender as follows: * 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female) * 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female) * 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female) * 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female) * 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female) * >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female) OR
  • Creatinine clearance >= 70 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
  • Corrected QT interval (QTc) =< 480 msec
  • Diarrhea < grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4
  • Fasting glucose < grade 2 (=< 160 mg/dL or =< 8.9 mmol/L) without the use of antihyperglycemic agents
  • Patients must be able to swallow either intact capsules or mini-tabs without chewing
  • In order to limit dose deviations due to rounding, patients must have a body surface area of at least 0.5 m^2
  • For patients with CNS tumors (primary or metastatic), any baseline neurologic deficits (including seizure) must be stable for at least one week prior to study enrollment
  • Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, using an institutionally approved informed consent procedure

Exclusion Criteria

  • Patients must not be receiving any of the following concomitant medications: * Pharmacologic doses of systemic corticosteroids unless for CNS metastatic or primary disease; for patients with CNS metastatic or primary tumors receiving corticosteroids, they should be on a stable or decreasing dose over the 7 days prior to registration; for all patients, receipt of systemic physiologic replacement steroids, topical, and/or inhaled corticosteroids is acceptable * Non-steroidal anti-inflammatory drugs, oral anticoagulants, and therapeutic heparins
  • Pregnant participants will not be entered on this study
  • Breastfeeding mothers are not eligible
  • Participants of child-bearing or child-fathering potential must agree to use adequate contraception (hormonal birth control; intrauterine device; double barrier method; or total abstinence) throughout their participation, including up until 30 days after last dose of CUDC-907
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CUDC-907
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; Note that patients who have had prior allogeneic transplantation are required to have cytomegalovirus (CMV) polymerase chain reaction (PCR) testing performed during screening; a positive screen would be evidence of an active infection and would render the patient ineligible
  • Patients with a known history of human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C (testing not required as part of screening)
  • Patients with a known history of type 1 or type 2 diabetes mellitus
  • Patients with gastrointestinal disease or disorder that could interfere with absorption of CUDC-907, such as bowel obstruction or inflammatory bowel disease


San Francisco
UCSF Medical Center-Parnassus
Status: ACTIVE
Contact: Kieuhoa Tran Vo
Phone: 415-476-3831


Boston Children's Hospital
Status: ACTIVE
Contact: Steven G. DuBois
Phone: 617-632-5460
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Steven G. DuBois
Phone: 617-632-5460


Children's Hospital of Philadelphia
Status: ACTIVE
Contact: Elizabeth Fox
Phone: 267-425-3010


Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Jodi Muscal
Phone: 832-824-4632


I. To determine the recommended pediatric phase 2 dose of fimepinostat (CUDC-907) in children and young adults with relapsed or refractory solid tumors, central nervous system (CNS) tumors, or lymphoma.

II. To describe the toxicities of CUDC-907 in this population.

III. To describe the pharmacokinetics of CUDC-907 in this population.


I. To describe the progression-free survival (PFS), objective response rate, and duration of response of CUDC-907 in this population, including expansion cohorts of patients with MYCN amplified / Myc-positive neuroblastoma, other solid tumors with MYC or MYCN amplification/high copy gain, or patients with mature B-cell lymphoma.


I. To evaluate the pharmacodynamic effects of CUDC-907 using peripheral blood as a surrogate tissue.

II. To explore potential tissue markers predictive of clinical benefit and resistance to CUDC-907.

III. To describe levels of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) at baseline and in response to CUDC-907.

IV. To bank remaining samples from correlative biology studies for potential future research.

OUTLINE: This is a dose-escalation study.

Patients receive fimepinostat orally (PO) once daily (QD) on days 1-5 of weeks 1-4. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Steven G. DuBois

  • Primary ID 16-371
  • Secondary IDs NCI-2016-01561
  • ID NCT02909777