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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00692354
• Date of registration: 04/06/2008
• Primary sponsor: Chroma Therapeutics
• Public title: Safety Study to Evaluate CHR-2797 in Patients With Advanced Tumours
• Scientific title: A Phase I Study to Evaluate the Safety and Tolerability, of the Aminopeptidase Inhibitor, CHR-2797, in Patients With Advanced Tumours
• Date of first enrolment: October 2004
• Target sample size: 41
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00692354
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Key inclusion & exclusion criteria

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:

1. Hb = 9.0 g/dl, absolute neutrophil count = 1.5 x 109/L, platelets = 100x109/L

2. Total bilirubin = 1.5 x upper normal limit

3. AST and ALT = 2.5 x upper normal limit (or = 5 x UNL in the presence of liver
metastases)

4. 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

1. History of congestive heart failure requiring therapy

2. History of unstable angina pectoris or myocardial infarction up to 6 months
prior to study entry

3. Presence of severe valvular heart disease

4. 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Advanced Solid Tumors

Intervention(s)

Drug: CHR-2797 (tosedostat)

Primary Outcome(s)

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. [Time Frame: 3 years]

Secondary Outcome(s)

To determine the PK parameters for oral CHR-2797 at increasing dose levels; [Time Frame: 3 years]

To enable a preliminary assessment of anti-tumour activity of CHR-2797 [Time Frame: 3 years]

To investigate the PD effects of CHR-2797 in blood and tumour cells [Time Frame: 3 years]

Secondary ID(s)

CHR-2797-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Institute of Cancer Research, United Kingdom