Phase I/II Dose-escalation Study to Investigate Safety and Pharmacokinetics/ Pharmacodynamics of WX-554 in Patients With Solid Tumours

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Wilex.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Wilex
ClinicalTrials.gov Identifier:
NCT01581060
First received: March 28, 2012
Last updated: November 27, 2012
Last verified: April 2012
  Purpose

The aim of part 1 of this study is to determine the optimal biological dose (OBD) and maximum tolerated dose (MTD) for WX-554 and the recommended dose/dose schedules for the chronic treatment in part 2. The aim of part 2 is to further determine the safety and tolerability of chronic treatment with WX-554.


Condition Intervention Phase
Advanced Solid Tumours
Drug: WX-554
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor WX-554 in Patients With Solid Tumours

Resource links provided by NLM:


Further study details as provided by Wilex:

Primary Outcome Measures:
  • Part 1: Determination of the Optimal Biological Dose (OBD) by the assessment of ERK phosphorylation (pERK) in peripheral blood mononuclear cells (PBMC) and assessment of TNF-alpha in plasma. [ Time Frame: Cycle 1 (21 days) ] [ Designated as safety issue: Yes ]
  • Part 1: Determination of the Maximum Tolerated Dose (MTD) for WX-554 by the evaluation of DLTs in 3-6 patients at the end of 1 treatment cycle [ Time Frame: Cycle 1 (21 days) ] [ Designated as safety issue: Yes ]
  • Part 2: To further determine the safety and tolerability by evaluating the incidence and severity of adverse events and serious adverse events (as per CTCAE grading), changes in hematology and chemistry values, vital signs, ECGs. [ Time Frame: expected average of 3-6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of PK variables maximum observed concentration (Cmax), minimum observed concentration (Cmin), time at which Cmax was present (tmax), Area Under Curve (AUC) [ Time Frame: PK profile on day 1 and day 8 ] [ Designated as safety issue: No ]
  • Assessment of ERK phosphorylation (pERK) in PBMC and tissue, assessment of TNF-alpha in plasma after oral intake of the OBD/MTD. [ Time Frame: expected average of 3-6 months ] [ Designated as safety issue: Yes ]
  • Tumour response evaluation using RECIST 1.1 [ Time Frame: expected average of 3-6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: March 2012
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: WX-554 Drug: WX-554
Capsules of WX-554

  Eligibility

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

Inclusion Criteria:

  1. Patients with advanced, metastatic and/or progressive solid tumours for whom there is no effective standard therapy available.
  2. Evaluable or measurable disease
  3. Has normal organ functions; is no greater than 2 on the ECOG Performance Scale
  4. life expectancy of >3 months
  5. negative hCG test in women of childbearing potential

Exclusion Criteria:

  1. Patients who received an investigational anti-cancer drug within 4 weeks of starting the study
  2. Patients who received major surgery, radiotherapy, or immunotherapy within 4 weeks of starting the study
  3. Clinically significant, unresolved toxicity from previous anti-cancer therapy Patients
  4. Patients who previously received a MEK inhibitor
  5. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
  6. Known medical history of retinal vein occlusion, intraocular pressure greater than 21 mm Hg or patient considered at risk of retinal vein thrombosis.
  7. Known HIV positivity or active hepatitis B or C infection.
  8. History of clinically significant cardiac condition
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01581060

Contacts
Contact: Carola Mala, PhD +49 (0)89-41 31 38 ext 50 carola.mala@wilex.com

Locations
United Kingdom
Queen's University Belfast Cancer Centre Recruiting
Belfast, United Kingdom, BT9 7AB
Principal Investigator: Richard Wilson, MD         
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom, G12 0YN
Principal Investigator: Jeff Evans, MD         
St James' Institute of Oncology Recruiting
Leeds, United Kingdom, LS9 7TF
Principal Investigator: Christopher Twelves, MD         
Christie NHS Foundation Trust, Oak Road Treatment Centre Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Malcolm Ranson, MD         
Sir Bobby Robson Cancer Trials Research Centre Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Contact: , PhD         
Principal Investigator: Ruth Plummer, MD         
Sponsors and Collaborators
Wilex
Investigators
Principal Investigator: Ruth Plummer, MD Sir Bobby Robson Cancer Trials Research Centre
  More Information

No publications provided

Responsible Party: Wilex
ClinicalTrials.gov Identifier: NCT01581060     History of Changes
Other Study ID Numbers: WX/80-003, 2011-003408-19
Study First Received: March 28, 2012
Last Updated: November 27, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014