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

NCT00572637 | Completed Phase 1

• 1 other identifier: E-CEP\I\01
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 3

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.

Conditions

Solid Tumors; Lymphoma, Non-Hodgkin

Outcome Measures

Primary Outcomes (1)

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

  Within the first 21-day cycle

Secondary Outcomes (3)

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

  Within the first 21-day cycle

• Profile and time course of inhibition and recovery of proteasome activity

  Within the first 21-day cycle

• Antineoplastic activity evaluated with internationally accepted response criteria

  throughout the study period

Interventions

CEP-18770 DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ethical Oncology Science: lead

Study Sites (3)

Europen Institute of Oncology

Milan, 20141, Italy

Location

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

Bellinzona, 6500, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

delanzomib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Cristiana Sessa, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 12, 2007
• First Posted: December 13, 2007
• Study Start: November 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 20, 2010

Record last verified: 2010-05

Locations

IT (1); CH (2)