Clinical trial NCT01905228: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Glioblastoma
Keywords: Metastatic Advance Solid Neoplasms
Unresectable Advance Solid Neoplasms
Lead sponsor: Incuron
Sponsor class: INDUSTRY
First posted: 2013-07-23
Enrollment: 83
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: San Antonio
country: United States
facility: CTRC at The University of Texas Healh Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: John Sarantopoulos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Roswell Park Cancer Institue
name: Renuka Iyer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Cleveland
name: Afshin Dowlati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Manmeet Ahluwalia, MD
role: PRINCIPAL_INVESTIGATOR
References: