Back to resultsA Phase 1 Trial of CBL0137 in Patients With Metastatic or Unresectable Advanced Solid Neoplasm
Primary Purpose
Solid Tumors, Glioblastoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CBL0137
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumors focused on measuring Metastatic Advance Solid Neoplasms, Unresectable Advance Solid Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Patients must have histological or cytological evidence of a solid neoplasm
- Patients enrolled in the expansion cohort must have at least one measureable lesion as defined by the RECIST 1.1 criteria for patients with systemic tumors or the RANO criteria for patients with gliomas;
Patients with a systemic tumor must:
- have metastatic or unresectable advanced solid tumors that have recurred or progressed following standard therapy or
- no longer be candidates for standard therapy or
- have tumors for which there is no standard therapy
Patients with a glioma must:
- have Grade III (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) disease, Grade IV (glioblastoma) disease, or diffuse intrinsic pontine glioma (DIPG) and;
- have received prior therapy including radiation and drug therapy and;
- have documented recurrent disease as defined in the RANO criteria;
- Patients must be ambulatory and have an ECOG Performance Score of 0 or 1;
- Patients or their legal representative must be able to provide written informed consent;
Patients must have adequate bone marrow reserve as evidenced by:
- White Blood Cell Count (WBC) > 3,000/µL
- Absolute Neutrophil Count (ANC) > 1,500/µL
- Platelet count (PLT) > 75,000/µL
- Hemoglobin (HGB) > 8.0 gm/dL (patients may be transfused to achieve this HGB level);
Patients must have adequate hepatic function as evidenced by:
- Serum AST/ALT < 3X the upper limit of normal (ULN) for the reference lab (< 5X the ULN for patients with known hepatic metastases)
- Serum bilirubin < 1.5 x the ULN for the reference lab;
Exclusion Criteria:
- Patients with active infection or with a fever > 38.50 C within 3 days of the first scheduled day of dosing;
- Patients with symptomatic CNS metastases who have not undergone surgery and/or radiotherapy and/or who are not neurologically stable;
- Patients with known hypersensitivity to any of the components of CBL0137;
- Patients who are receiving concurrent anticancer therapy;
- Patients receiving enzyme-inducing antiepileptic agents within 14 days prior to the start of study therapy;
- Males with mean QTcF values of > 450 msec and females with QTcF values of > 470 msec following 3 ECGs conducted 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes; or patients who are on medications known to cause prolonged QT intervals on ECG;
Please speak with the PI for the complete Inclusion/Exclusion listing.
Sites / Locations
- Roswell Park Cancer Institute
- University Hospital of Cleveland
- Cleveland Clinic
- CTRC at The University of Texas Healh Science Center at San Antonio
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CBL0137
Arm Description
Dose Level 9: 150 mg/m2, IV Dose Level 10: 180 mg/m2, IV Dose Level 11: 240 mg/m2, IV Dose Level 12: 320 mg/m2, IV Dose Level 13: 400 mg/m2, IV Dose Level 14: 540 mg/m2, IV Dose Level 15: 700 mg/m2, IV Dose Level 16: 920 mg/m2, IV Dose Level 17: 1200 mg/m2, IV Dose Level 18: 1600 mg/m2, IV Dose Level 19: 2100 mg/m2, IV Dose Level 20: 2700 mg/m2, IV
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
MTD is defined as dose level at which ≥6 participants have been treated and which is associated with a first-cycle DLT in ≤17% of the participants. Selection of RP2D from within the tolerated dose range will be based on evaluation of short- and long-term safety information together with findings relating to compliance, pharmacokinetics, pharmacodynamics and antitumor activity.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01905228
Brief Title
A Phase 1 Trial of CBL0137 in Patients With Metastatic or Unresectable Advanced Solid Neoplasm
Official Title
A Phase 1 Trial of CBL0137 in Patients With Metastatic or Unresectable Advanced Solid Neoplasm
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
May 2019 (Actual)
Study Completion Date
June 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incuron
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open-label, multi-center, sequential groups, dose-escalation study of CBL0137 administered intravenously in participants with metastatic or unresectable advanced solid malignancies.
Detailed Description
The primary objective of the study is to determine the maximally tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of CBL0137. The secondary objectives are to describe the dose-limiting toxicity (DLT) and adverse event profile of CBL0137, to describe the pharmacokinetic profile of CBL0137, to document any objective responses to CBL0137. This is a study of CBL0137 with a standard "3+3" design. Escalation will proceed to the MTD based on DLT in the 1st cycle in 1 of 6 participants in a cohort.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Glioblastoma
Keywords
Metastatic Advance Solid Neoplasms, Unresectable Advance Solid Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CBL0137
Arm Type
Experimental
Arm Description
Dose Level 9: 150 mg/m2, IV
Dose Level 10: 180 mg/m2, IV
Dose Level 11: 240 mg/m2, IV
Dose Level 12: 320 mg/m2, IV
Dose Level 13: 400 mg/m2, IV
Dose Level 14: 540 mg/m2, IV
Dose Level 15: 700 mg/m2, IV
Dose Level 16: 920 mg/m2, IV
Dose Level 17: 1200 mg/m2, IV
Dose Level 18: 1600 mg/m2, IV
Dose Level 19: 2100 mg/m2, IV
Dose Level 20: 2700 mg/m2, IV
Intervention Type
Drug
Intervention Name(s)
CBL0137
Other Intervention Name(s)
Curaxin
Intervention Description
All doses are administered intravenously on Days 1, 8 and 15 of every 28 day cycle.
Number of Cycles: 2 or until progression or unacceptable toxicity develops
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
Description
MTD is defined as dose level at which ≥6 participants have been treated and which is associated with a first-cycle DLT in ≤17% of the participants. Selection of RP2D from within the tolerated dose range will be based on evaluation of short- and long-term safety information together with findings relating to compliance, pharmacokinetics, pharmacodynamics and antitumor activity.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have histological or cytological evidence of a solid neoplasm
Patients enrolled in the expansion cohort must have at least one measureable lesion as defined by the RECIST 1.1 criteria for patients with systemic tumors or the RANO criteria for patients with gliomas;
Patients with a systemic tumor must:
have metastatic or unresectable advanced solid tumors that have recurred or progressed following standard therapy or
no longer be candidates for standard therapy or
have tumors for which there is no standard therapy
Patients with a glioma must:
have Grade III (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) disease, Grade IV (glioblastoma) disease, or diffuse intrinsic pontine glioma (DIPG) and;
have received prior therapy including radiation and drug therapy and;
have documented recurrent disease as defined in the RANO criteria;
Patients must be ambulatory and have an ECOG Performance Score of 0 or 1;
Patients or their legal representative must be able to provide written informed consent;
Patients must have adequate bone marrow reserve as evidenced by:
White Blood Cell Count (WBC) > 3,000/µL
Absolute Neutrophil Count (ANC) > 1,500/µL
Platelet count (PLT) > 75,000/µL
Hemoglobin (HGB) > 8.0 gm/dL (patients may be transfused to achieve this HGB level);
Patients must have adequate hepatic function as evidenced by:
Serum AST/ALT < 3X the upper limit of normal (ULN) for the reference lab (< 5X the ULN for patients with known hepatic metastases)
Serum bilirubin < 1.5 x the ULN for the reference lab;
Exclusion Criteria:
Patients with active infection or with a fever > 38.50 C within 3 days of the first scheduled day of dosing;
Patients with symptomatic CNS metastases who have not undergone surgery and/or radiotherapy and/or who are not neurologically stable;
Patients with known hypersensitivity to any of the components of CBL0137;
Patients who are receiving concurrent anticancer therapy;
Patients receiving enzyme-inducing antiepileptic agents within 14 days prior to the start of study therapy;
Males with mean QTcF values of > 450 msec and females with QTcF values of > 470 msec following 3 ECGs conducted 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes; or patients who are on medications known to cause prolonged QT intervals on ECG;
Please speak with the PI for the complete Inclusion/Exclusion listing.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Sarantopoulos, MD
Organizational Affiliation
The University of Texas Health Science Center at San Antonio
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Renuka Iyer, MD
Organizational Affiliation
Roswell Park Cancer Institue
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Afshin Dowlati, MD
Organizational Affiliation
University Hospital of Cleveland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Manmeet Ahluwalia, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
University Hospital of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
CTRC at The University of Texas Healh Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 1 Trial of CBL0137 in Patients With Metastatic or Unresectable Advanced Solid Neoplasm
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