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

NCT01581060 | Terminated Phase 1

• 2 other identifiers: WX/80-0032011-003408-19
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Advanced Solid Tumours

Outcome Measures

Primary Outcomes (3)

• 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.

  Cycle 1 (21 days)

• 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

  Cycle 1 (21 days)

• 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.

  expected average of 3-6 months

Secondary Outcomes (3)

• Assessment of PK variables maximum observed concentration (Cmax), minimum observed concentration (Cmin), time at which Cmax was present (tmax), Area Under Curve (AUC)

  PK profile on day 1 and day 8

• Assessment of ERK phosphorylation (pERK) in PBMC and tissue, assessment of TNF-alpha in plasma after oral intake of the OBD/MTD.

  expected average of 3-6 months

• Tumour response evaluation using RECIST 1.1

  expected average of 3-6 months

Study Arms (1)

WX-554

EXPERIMENTAL

Drug: WX-554

Interventions

WX-554 DRUG

Capsules of WX-554

WX-554

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients who received an investigational anti-cancer drug within 4 weeks of starting the study
• Patients who received major surgery, radiotherapy, or immunotherapy within 4 weeks of starting the study
• Clinically significant, unresolved toxicity from previous anti-cancer therapy Patients
• Patients who previously received a MEK inhibitor
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
• Known medical history of retinal vein occlusion, intraocular pressure greater than 21 mm Hg or patient considered at risk of retinal vein thrombosis.
• Known HIV positivity or active hepatitis B or C infection.
• History of clinically significant cardiac condition

Sponsors & Collaborators

• Heidelberg Pharma AG: lead

Study Sites (5)

Queen's University Belfast Cancer Centre

Belfast, BT9 7AB, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

St James' Institute of Oncology

Leeds, LS9 7TF, United Kingdom

Location

Christie NHS Foundation Trust, Oak Road Treatment Centre

Manchester, M20 4BX, United Kingdom

Location

Sir Bobby Robson Cancer Trials Research Centre

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Study Officials

• Ruth Plummer, MD

  Sir Bobby Robson Cancer Trials Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: April 19, 2012
• Study Start: March 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 16, 2014

Record last verified: 2014-05

Locations

GB (5)