Clinical Trials /

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

NCT02909777

Description:

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.

Related Conditions:
  • Burkitt Lymphoma
  • Central Nervous System Neoplasm
  • Diffuse Large B-Cell Lymphoma
  • Lymphoma
  • Neuroblastoma
  • Solid Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma
  • Official Title: Phase 1 Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 16-371
  • NCT ID: NCT02909777

Conditions

  • Lymphoma
  • Neuroblastoma
  • Brain Tumor
  • Solid Tumor

Interventions

DrugSynonymsArms
CUDC-907CUDC-907

Purpose

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.

Detailed Description

      This is a Phase I clinical trial. A Phase I clinical trial tests the safety of an
      investigational intervention and also tries to find the best dose of the investigational
      intervention to use for further studies. "Investigational" means that the intervention is
      being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved CUDC-907 as a treatment
      option for any disease.

      This is the first time that CUDC-907 will be given to children.

      In this research study, the investigators are evaluating a new drug, CUDC-907, as a potential
      new treatment for children with solid tumors, lymphomas and brain tumors. CUDC-907 is an oral
      drug that blocks certain proteins in tumor cells. These proteins may be important in the
      growth of some cancers. Laboratory experiments and results from adult studies demonstrate
      that CUDC-907 may stop tumor growth and, in some cases, cause tumor cells to die. CUDC-907
      has been tested in adults with cancer to find out about side effects and dosing in adults.
      The primary goal of this study is to evaluate side effects of CUDC-907 and find the best dose
      of CUDC-907 when used in children. Other goals of this study are to determine whether this
      drug may have benefits against the types of cancer seen in children and to measure the
      effects of CUDC-907 in the blood.
    

Trial Arms

NameTypeDescriptionInterventions
CUDC-907ExperimentalCUDC-907 orally administered CUDC-907 once daily for 5 consecutive days per week followed by two days without dosing Dose level assigned at registration Pre-dose pharmacokinetic blood sample will be collected Dose escalation will follow a standard 3+3 design
  • CUDC-907

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
             confirmed:

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

                    -  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
                       Laboratory.

               -  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
             chair.

          -  Monoclonal antibody: At least 21 days after the last dose of anitbody

          -  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 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
             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
             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 CMV 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 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.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Peak plasma concentration of CUDC-907 in Pediatrics
Time Frame:2 years
Safety Issue:
Description:Determined using standard methods and reported descriptively in aggregate and by assigned dose level.
Measure:Exposure (AUC) of CUDC-907 in Pediatrics
Time Frame:2 years
Safety Issue:
Description:Determined using standard methods and reported descriptively in aggregate and by assigned dose level.
Measure:Duration of Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Adverse Events per CTCAE Version 4
Time Frame:2 years
Safety Issue:
Description:
Measure:Objective Response
Time Frame:2 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Lymphoma
  • Neuroblastoma
  • Brain Tumor
  • Solid Tumor

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