Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma

Status: Recruiting
Phase: Phase 1
DFCI Protocol ID: 16-371

This research study is evaluating a novel drug called CUDC-907 as a possible treatment for resistant (refractory) pediatric solid tumors (including neuroblastoma), lymphoma, or brain tumors.

Conducting Institutions:

Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

Steven Dubois MD, Dana Farber Cancer Institute

Site-responsible Investigators:


Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,

Eligibility Criteria

Inclusion Criteria:

  -  Age > 1 years and ≤ 21 years at time of enrollment.

  -  Karnofsky performance status ≥ 50% for patients ≥16 years of age and Lansky ≥ 50% for
     patients <16 years of age (see Appendix A)

  -  Diagnosis requirement

  -  For Parts A and B, participants must have evaluable or measurable disease (see
     Section 11).

  -  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

       -  Neuroblastoma with evidence of Mycn/Myc positivity based on any of the

    -  MYCN amplification (> 4 copy amplification) from COG reference laboratory
       or other 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

       -  One of the following mature B cell lymphoma diagnoses:

    -  Diffuse large B cell lymphoma

    -  Burkitt lymphoma

  -  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 as noted in Section 3.1.6). Patients must
     meet the following minimum washout periods prior to enrollment:

  -  Myelosuppressive chemotherapy: 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 XRT (small port);

       -  At least 90 days must have elapsed after prior TBI, craniospinal XRT or if >50%
  radiation of pelvis;

       -  At least 42 must have elapsed if other substantial BM radiation;

       -  At least 42 days must have passed since last MIBG or other radionuclide therapy.

  -  Small molecule biologic 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

  -  Monoclonal antibody: At least 21 days or 3 half-lives of the antibody after the last
     dose, whichever is longer.

  -  Myeloid growth factors: At least 14 days following the last dose of long-acting
     growth factor (e.g. Neulasta) or 7 days following short-acting growth factor.

  -  Stem Cell Infusion or Cellular Therapies: 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.

  -  Major Surgery: At least 3 weeks from prior major surgical procedure. Note: Biopsy and
     central line placement/removal are not considered major.

  -  PI3K and HDAC inhibitors: 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.

  -  Participants must have normal organ function as defined below.

  -  Bone Marrow Function:

       -  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 CBC documenting eligibility.

  -  Hepatic Function:

       -  Total bilirubin ≤ 1.5 x upper limit of normal for age

       -  ALT (SGPT) ≤ 135 U/L For the purpose of this study, the ULN for ALT is 45 U/L

       -  Serum albumin > 2 g/dL

  -  Renal Function:

     --A serum creatinine based on age/gender as follows: Age Maximum Serum Creatinine
     (mg/dL) Male Female

       1. to < 2 years 0.6 0.6

       2. to < 6 years 0.8 0.8

     6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

     ≥ 16 years 1.7 1.4 OR

     --Creatinine clearance ≥ 70 mL/min/1.73 m2 for participants with creatinine levels
     above institutional normal.

  -  Adequate Cardiac Function: QTc < 480 msec

  -  Adequate GI Function: Diarrhea < grade 2 by CTCAE version 4

  -  Adequate Metabolic Function: Fasting glucose < grade 2 (< 160 mg/dL or < 8.9 mmol/L)
     without the use of antihyperglycemic agents.

  -  Additional Agent-Specific Requirements

  -  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 m2

  -  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

  -  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 and meet criteria.

  -  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 given that the effects of
     CUDC-907 on the developing human fetus are unknown.

  -  Because there is an unknown but potential risk for adverse events in nursing infants
     secondary to treatment of the mother with CUDC-907, breastfeeding mothers are not

  -  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.

  -  Patients with a known history of 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.

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