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Phase I Study of the Proteosome Inhibitor CEP 18770 in Patients With Solid Tumours or Non-Hodgkin's Lymphomas

Primary Purpose

Solid Tumors, Lymphoma, Non-Hodgkin

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

CEP-18770

About this trial

This is an interventional treatment trial for Solid Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

diagnosis of relapsed or refractory solid tumour or non-Hodgkin's lymphoma
unresponsive or poorly responsive to accepted treatment modalities
expected survival of at least 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
fully recovered from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, and immunotherapy (exceptions: alopecia and grade 1 neurotoxicity).
al least 4 weeks from last cancer therapy (or 6 weeks from previous mitomycin C; 2 weeks from previous biological therapy; 8 weeks from previous bevacizumab)
no more than 3 previous chemotherapies for advanced disease (excluding TKIs)
good health as determined by a medical and psychiatric history, medical examination, ECG, serum chemistry, hematology, urinalysis, and serology.
for women of childbearing potential use of a medically accepted method of contraception for the duration of the study and for 60 days after the last administration of study drug
for men not surgically sterile use of an accepted method of birth control for the duration of the study and for 60 days after the last administration of study drug
willingness and ability to comply with study requirements

Exclusion Criteria:

Any of the following hematologic values: absolute neutrophil count (ANC) less than 1500/mm3, platelet count less than 100,000/mm3, or hemoglobin less than 9 g/dL
Any of the following hepatic function values: bilirubin greater than 1.5 times the upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the ULN
Serum creatinine value greater than 1.5 mg/dL.
Known cerebral metastases or active CNS disease
Signs indicating potential major bone marrow involvement
Significant neurotoxicity (higher than grade 1 as defined by NCI-CTC scale v. 3.0 and/or a TNSc value ≥ 3)
Any concomitant cancer related treatment. (Continuing endocrine treatment at stable doses is allowed; treatment must be ongoing for at least 4 weeks)
Concomitant treatment with steroids
Previous treatment with high-dose chemotherapy with PBSC support
Any investigational drug within the past 4 weeks
Any medications which are human cytochrome P450 34A (CYP3A4) substrates within 1 week, or 5 half-lives (whichever is longer) before the first administration of study drug or need for continuous treatment with these medications during the study
Known hypersensitivity to boronic acid derivatives or excipients in the CEP-18770 formulation.
Any condition which, in the judgment of the Investigator, would place the subject at undue risk or interfere with the results of the study, or make the subject otherwise unsuitable (e.g., risk factors for neurological toxicities)

Sites / Locations

Europen Institute of Oncology
IOSI - Oncology Institute of Southern Switzerland - Ospedale S. Giovanni
Kantonsspital St. Gallen

Outcomes

Primary Outcome Measures

Dose Limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of CEP 18770

Secondary Outcome Measures

Pharmacokinetics of CEP-18770 following single and multiple dose administration.

Profile and time course of inhibition and recovery of proteasome activity

Antineoplastic activity evaluated with internationally accepted response criteria

Full Information

NCT ID

NCT00572637

First Posted

December 12, 2007

Last Updated

May 19, 2010

Sponsor

Ethical Oncology Science

1. Study Identification

Unique Protocol Identification Number

NCT00572637

Brief Title

Phase I Study of the Proteosome Inhibitor CEP 18770 in Patients With Solid Tumours or Non-Hodgkin's Lymphomas

Official Title

An Open-Label, Dose-escalation, Phase I Study to Determine the Maximum Tolerated Dose, Recommended Dose, Pharmacokinetics, and Pharmacodynamics of the Proteosome Inhibitor CEP 18770 Given Intravenously as Single Agent in Patients With Advanced Solid Tumours or Non-Hodgkin's Lymphomas

Study Type

Interventional

2. Study Status

Record Verification Date

May 2010

Overall Recruitment Status

Completed

Study Start Date

November 2007 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Ethical Oncology Science

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This Phase 1 escalating-dose study is designed to assess, the safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel proteasome inhibitor CEP 18770, given intravenously as single agent, in patients with advanced, incurable solid tumours or NHL, and to identify the recommended dose of CEP 18770 to be used in Phase 2 studies.

Detailed Description

This is an open-label, multicenter, dose-escalating study to determine the MTD and dose limiting toxicities (DLTs) of CEP 18770, a novel proteasome inhibitor. The study will also characterize the pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of CEP 18770, and assess the safety and tolerability of CEP-18770 treatment as well as any effect on tumour response whenever possible. Patients will be treated intravenously with CEP 18770 on days 1, 4, 8, and 11 of a 21-day cycle period. Additional cycles may be administered, up to 6, as long as patients are maintaining their performance status and appear to be receiving clinical benefit from the study. Safety data will be collected for all patients in order to determine the toxicity and reversibility of toxicity of CEP 18770. Formal assessments will be performed throughout the study including at baseline, prior to each dose of study medication every week, and 30 days following the last dose of study drug. Patients with drug-related toxicities will continue to be reviewed until resolution or stabilization of the toxicity. Pharmacokinetic and pharmacodynamic parameters will also be assessed in each cohort of patients during cycle 1. Where applicable, tumour measurements will be documented and any observed anti-tumour activity will be evaluated. The study will follow a conventional MTD design with patients recruited in cohorts of 3 patients, with criteria to expand to 6 patients. Enrolment for each cohort will begin when the required number of patients in the prior cohort have completed one 21-day cycle of study drug treatment at the current dose level without experiencing a DLT. Once the MTD has been determined, additional 10 patients will be treated at the MTD to further explore the toxicity of this dose, and its suitability for Phase II studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumors, Lymphoma, Non-Hodgkin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

55 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

CEP-18770

Intervention Description

Administered as intravenous infusion on days 1, 4, 8, and 11 of a 21-day cycle up to 6 cycles. Starting dose 0,1 mg/sqm

Primary Outcome Measure Information:

Title

Dose Limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of CEP 18770

Time Frame

Within the first 21-day cycle

Secondary Outcome Measure Information:

Title

Pharmacokinetics of CEP-18770 following single and multiple dose administration.

Time Frame

Within the first 21-day cycle

Title

Profile and time course of inhibition and recovery of proteasome activity

Time Frame

Within the first 21-day cycle

Title

Antineoplastic activity evaluated with internationally accepted response criteria

Time Frame

throughout the study period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: diagnosis of relapsed or refractory solid tumour or non-Hodgkin's lymphoma unresponsive or poorly responsive to accepted treatment modalities expected survival of at least 12 weeks Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 fully recovered from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, and immunotherapy (exceptions: alopecia and grade 1 neurotoxicity). al least 4 weeks from last cancer therapy (or 6 weeks from previous mitomycin C; 2 weeks from previous biological therapy; 8 weeks from previous bevacizumab) no more than 3 previous chemotherapies for advanced disease (excluding TKIs) good health as determined by a medical and psychiatric history, medical examination, ECG, serum chemistry, hematology, urinalysis, and serology. for women of childbearing potential use of a medically accepted method of contraception for the duration of the study and for 60 days after the last administration of study drug for men not surgically sterile use of an accepted method of birth control for the duration of the study and for 60 days after the last administration of study drug willingness and ability to comply with study requirements Exclusion Criteria: Any of the following hematologic values: absolute neutrophil count (ANC) less than 1500/mm3, platelet count less than 100,000/mm3, or hemoglobin less than 9 g/dL Any of the following hepatic function values: bilirubin greater than 1.5 times the upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the ULN Serum creatinine value greater than 1.5 mg/dL. Known cerebral metastases or active CNS disease Signs indicating potential major bone marrow involvement Significant neurotoxicity (higher than grade 1 as defined by NCI-CTC scale v. 3.0 and/or a TNSc value ≥ 3) Any concomitant cancer related treatment. (Continuing endocrine treatment at stable doses is allowed; treatment must be ongoing for at least 4 weeks) Concomitant treatment with steroids Previous treatment with high-dose chemotherapy with PBSC support Any investigational drug within the past 4 weeks Any medications which are human cytochrome P450 34A (CYP3A4) substrates within 1 week, or 5 half-lives (whichever is longer) before the first administration of study drug or need for continuous treatment with these medications during the study Known hypersensitivity to boronic acid derivatives or excipients in the CEP-18770 formulation. Any condition which, in the judgment of the Investigator, would place the subject at undue risk or interfere with the results of the study, or make the subject otherwise unsuitable (e.g., risk factors for neurological toxicities)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cristiana Sessa, MD, PhD

Organizational Affiliation

Oncology Institute of Southern Switzerland - Ospedale S. Giovanni Bellinzona CH

Official's Role

Principal Investigator

Facility Information:

Facility Name

Europen Institute of Oncology

City

Milano

ZIP/Postal Code

20141

Country

Italy

Facility Name

IOSI - Oncology Institute of Southern Switzerland - Ospedale S. Giovanni

City

Bellinzona

ZIP/Postal Code

6500

Country

Switzerland

Facility Name

Kantonsspital St. Gallen

City

St. Gallen

ZIP/Postal Code

9007

Country

Switzerland

12. IPD Sharing Statement

Learn more about this trial

Phase I Study of the Proteosome Inhibitor CEP 18770 in Patients With Solid Tumours or Non-Hodgkin's Lymphomas

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