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

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ethical Oncology Science
• Treatments: Delanzomib; Proteasome Inhibitors

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)