A Study of the Safety and Tolerability of the Addition of CHR-2797 to Paclitaxel in Patients With Advanced or Refractory Tumours

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chroma Therapeutics
ClinicalTrials.gov Identifier:
NCT00737555
First received: August 18, 2008
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

The treatment of cancer often involves the use of more than one drug at the same time. In this study, patients are treated with the already marketed drug paclitaxel (administered every 3 weeks by infusion)and with the investigational drug CHR-2797 (given orally, once daily). The purpose of this study is to evaluate if it is safe to administer these two drugs together, and how well the combination is tolerated by patients. The first patients will receive a 90mg dose of CHR-2797; doses will be increased in subsequent patients, as long as they are adequately tolerated.


Condition Intervention Phase
Solid Tumor
Drug: CHR-2797
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Dose-escalation Study to Evaluate the Safety and Tolerability of the Addition of the Aminopeptidase Inhibitor CHR-2797 to Paclitaxel in Patients With Advanced or Refractory Tumours

Resource links provided by NLM:


Further study details as provided by Chroma Therapeutics:

Primary Outcome Measures:
  • To determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered in combination with paclitaxel. [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetic profile of the combination of CHR-2797 and paclitaxel and identify any pharmacokinetic interaction between the 2 agents. [ Time Frame: After 1st and 2nd infusion of paclitaxel ] [ Designated as safety issue: Yes ]
  • To determine response and response duration, time to progressive disease or treatment failure during combination therapy and in those patients who continued beyond 18 weeks on monotherapy with CHR-2797. [ Time Frame: Maximum duration of patient treatment ( combination followed by monotherapy) was 9 months ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: August 2006
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Once daily oral administration of CHR-2797 ( escalating dose groups) in solid tumour patients receiving paclitaxel infusion every three weeks
Drug: CHR-2797
Oral once daily administration of capsules of CHR-2797, to determine safety and tolerability in patients being treated with paclitaxel infusion every 3 weeks for up to 18 weeks.
Other Names:
  • Aminopeptidase inhibitor
  • Proposed INN: tosedostat

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed, informed consent.
  • Age > 18 years
  • Histologically or cytologically documented locally advanced or metastatic solid tumour refractory to standard therapy or for which no standard therapy exists.
  • Patients should have recovered from the acute adverse effects of prior therapies (excluding alopecia).
  • Adequate bone marrow, hepatic and renal function including the following:
  • Hb > 9g/dl (transfusion independent) or >10g/dl (transfusion permitted), absolute neutrophil count > 1.5 x 109/L, platelets ≥ 100 x 109/L;
  • Total bilirubin ≤ 1.5 x upper normal limit;
  • AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit
  • Creatinine ≤1.5 x upper normal limit.
  • Performance status (PS) ≤ 2 (ECOG scale).
  • Estimated life-expectancy greater than 3 months.
  • Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment.

Exclusion Criteria:

  • Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to first dose of medication in this trial or within a longer period, depending on the defined characteristics of the agent e.g. 6 weeks for nitrosurea or mitomycin. Bisphosphonates for bone disease are permitted provided the doses are stable before and during the trial.
  • 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 trial 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 will
  • substantially increase 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 may interfere with absorption of the study drug.
  • Persistent grade II or greater toxicity from any cause.
  • Patients with known brain tumours or metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events.
  • More than 4 prior chemotherapy regimens.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00737555

Locations
Netherlands
UMC St Radboud
Nijmegen, Netherlands, 6525 GA
Erasmus MC University Medical Centre- Location Centrum
Rotterdam, Netherlands, 3015 CE
Sponsors and Collaborators
Chroma Therapeutics
Investigators
Principal Investigator: Carla van Herpen UMC St Radboud
Principal Investigator: Ferry Eskens Erasmus MC University Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Chroma Therapeutics
ClinicalTrials.gov Identifier: NCT00737555     History of Changes
Other Study ID Numbers: CHR-2797-003, EudraCT# 2006-002498-35
Study First Received: August 18, 2008
Last Updated: February 14, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Chroma Therapeutics:
Solid tumour
Solid tumor
Pharmacokinetic
Interaction
dose escalation
cancer
paclitaxel

Additional relevant MeSH terms:
Neoplasms
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014