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

Primary Purpose

Lymphoma, Neuroblastoma, Brain Tumor

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CUDC-907
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Lymphoma, Neuroblastoma, Brain Tumor, Solid Tumor

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California, San Francisco, Benioff Children's Hospital
  • Dana Farber Cancer Institute
  • Children's Hospital of Philadelphia
  • Texas Children's, Baylor College of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CUDC-907

Arm Description

CUDC-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

Outcomes

Primary Outcome Measures

Dose Limiting Toxicity

Secondary Outcome Measures

Progression Free Survival
Peak plasma concentration of CUDC-907 in Pediatrics
Determined using standard methods and reported descriptively in aggregate and by assigned dose level.
Exposure (AUC) of CUDC-907 in Pediatrics
Determined using standard methods and reported descriptively in aggregate and by assigned dose level.
Duration of Response
Adverse Events per CTCAE Version 4
Objective Response

Full Information

First Posted
September 13, 2016
Last Updated
August 7, 2023
Sponsor
Dana-Farber Cancer Institute
Collaborators
Curis, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02909777
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2016 (undefined)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Curis, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Neuroblastoma, Brain Tumor, Solid Tumor
Keywords
Lymphoma, Neuroblastoma, Brain Tumor, Solid Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CUDC-907
Arm Type
Experimental
Arm Description
CUDC-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
Intervention Type
Drug
Intervention Name(s)
CUDC-907
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression Free Survival
Time Frame
2 years
Title
Peak plasma concentration of CUDC-907 in Pediatrics
Description
Determined using standard methods and reported descriptively in aggregate and by assigned dose level.
Time Frame
2 years
Title
Exposure (AUC) of CUDC-907 in Pediatrics
Description
Determined using standard methods and reported descriptively in aggregate and by assigned dose level.
Time Frame
2 years
Title
Duration of Response
Time Frame
2 years
Title
Adverse Events per CTCAE Version 4
Time Frame
2 years
Title
Objective Response
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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 to < 2 years 0.6 0.6 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David S Shulman, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco, Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Texas Children's, Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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