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

This study has been completed.
Sponsor:
Collaborator:
Institute of Cancer Research, United Kingdom
Information provided by:
Chroma Therapeutics
ClinicalTrials.gov Identifier:
NCT00692354
First received: June 4, 2008
Last updated: August 5, 2010
Last verified: June 2008

June 4, 2008
August 5, 2010
October 2004
November 2007   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00692354 on ClinicalTrials.gov Archive Site
  • To determine the PK parameters for oral CHR-2797 at increasing dose levels; [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To investigate the PD effects of CHR-2797 in blood and tumour cells [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To enable a preliminary assessment of anti-tumour activity of CHR-2797 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Safety Study to Evaluate CHR-2797 in Patients With Advanced Tumours
A Phase I Study to Evaluate the Safety and Tolerability, of the Aminopeptidase Inhibitor, CHR-2797, in Patients With Advanced Tumours

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.
Not Provided
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Advanced Solid Tumors
Drug: CHR-2797 (tosedostat)
Drug was given orally, once daily, ensuring a dosing interval of approximately 24 hours. Dose escalations took place starting at 10mg and escalating (per protocol) as follows: 20, 40, 90, 130, 180, 240 and 320 mg
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
March 2008
November 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00692354
CHR-2797-001
Yes
Dr Leon Hooftman, Chroma Therapeutics Ltd
Chroma Therapeutics
Institute of Cancer Research, United Kingdom
Not Provided
Chroma Therapeutics
June 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP