Safety Study to Evaluate CHR-2797 in Patients With Advanced Tumours

Sponsor

Chroma Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00692354

Collaborator

Institute of Cancer Research, United Kingdom (Other)

Enrollment

Duration (Months)

Study Details

Study Description

Brief Summary

The primary objective of this study was to determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily, to patients with advanced solid tumours.

The secondary objectives of this study were:

To determine pharmacokinetic parameters for CHR-2797 when administered orally at increasing dose levels;
To investigate the pharmacodynamic effects of CHR-2797 in blood mononuclear cells and, when possible, tumour cells; - To enable a preliminary assessment of anti-tumour activity of CHR-2797.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: CHR-2797 (tosedostat)	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study to Evaluate the Safety and Tolerability, of the Aminopeptidase Inhibitor, CHR-2797, in Patients With Advanced Tumours

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Mar 1, 2008

Outcome Measures

Primary Outcome Measures

To determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily, to patients with advanced solid tumours. [3 years]

Secondary Outcome Measures

To determine the PK parameters for oral CHR-2797 at increasing dose levels; [3 years]
To investigate the PD effects of CHR-2797 in blood and tumour cells [3 years]
To enable a preliminary assessment of anti-tumour activity of CHR-2797 [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed, informed consent
Histological or cytologically confirmed malignant solid tumour refractory to standard therapy or for which no standard therapy exists
Evaluable disease
Recovered from the acute adverse effects of prior therapies (excluding alopecia and grade 1 neuropathy)
Adequate bone marrow, hepatic and renal function including the following:

Hb ≥ 9.0 g/dl, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 100x109/L
Total bilirubin ≤ 1.5 x upper normal limit
AST and ALT ≤ 2.5 x upper normal limit (or ≤ 5 x UNL in the presence of liver metastases)
Creatinine ≤1.5 x upper normal limit

Age < 18 years
Performance status (PS) < 2 (ECOG scale)
Estimated life expectancy greater than 3 months
Female patients with reproductive potential had to have a negative serum pregnancy test within 7 days of treatment. Both women and men had to agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception included IUD, oral contraceptive, sub-dermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary)

Exclusion Criteria:

Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to study entry (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea). In patients with progressive disease (PD), continuation of LHRH agonists for prostate cancer, bisphosphonates for bone disease and corticosteroids was permitted provided the dose was stable before and during the study
Co-existing active infection or serious concurrent illness
Significant cardiovascular disease as defined by

History of congestive heart failure requiring therapy
History of unstable angina pectoris or myocardial infarction up to 6 months prior to study entry
Presence of severe valvular heart disease
Presence of a ventricular arrhythmia requiring treatment

Any co-existing medical condition that in the Investigator's judgement substantially increased the risk associated with the patient's participation in the study
Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
Gastrointestinal disorders that might have interfered with absorption of the study drug
Persistent grade 2 or greater toxicities from any cause
Patients with known brain tumours or metastases should have been excluded from this clinical study because of their poor prognosis and because they often develop progressive neurologic dysfunction that would have confounded the evaluation of neurologic and other AEs
Pregnant or breast-feeding women