Safety of CHIR-258 (TKI258) in Advanced Solid Tumors

January 4, 2011 updated by: Novartis Pharmaceuticals

A Phase 1 Dose Escalating Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodyniamics of CHIR-258 in Subjects With Advanced Solid Tumor Malignancies

Phase I dose finding study in solid tumors.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Glasgow, United Kingdom
        • Novartis Investigative Site
      • Sutton, United Kingdom
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of histologically or cytologically documented, advanced-stage, primary or metastatic solid tumors that are refractory to standard therapy or for which no curative standard therapy exists.
  • Evidence of measurable or evaluable disease.
  • All acute toxic affects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade ≤1; surgery must have occurred at least 28 days prior to study enrollement.
  • Age must be at least 18 years.
  • Last dose of antineoplastic therapy (except for hormonal therapy) must be more than 21 days; subjects may continue to receive luteinizing hormone-releasing hormone analog therapy for prostate cancer.
  • ECOG performance status must be 0 or 1.
  • Life expectancy of at least 3 months.
  • Patient must meet protocol-specified laboratory values.

Exclusion Criteria:

  • Concurrent therapy with any other investigational agent.
  • Intracranial edema, intracranial metastasis, or epidural disease.
  • Pregnant or breastfeeing women. Female subjects must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male subjects must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the investigator or a designated associate. All at-risk female subjects must have a netative pregnancy test (serum or urine) within 10 days prior to the start of study treatment.
  • Clinically significant cardiac disease (New York Heart Association Class III or IV) including pre-existing arrhythmia, congestive heart failure, cardiomyopathy, or subjects with baseline mean QTc interval greater than 450 msec (males) and 470 msec (females) or grade 2 or higher compromised left ventricular ejection fraction (LVEF) as determined by MUGA or ECHO.
  • Dementia or altered mental status that would prohibit informed consent.
  • Diabetes mellitus (insulin-dependent or -independent disease requiring chronic medication).
  • Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month.
  • Malabsorption syndrome or uncontrolled gastrointestinal toxicities (nausea, diarrhea, vomitting) with toxicity greater than NCI CTCAE grade 2.
  • Prior acute or chonic pancreatitis of any etiology.
  • Prior intra-or extra-hepatic biliary obstruction wtihin the previous 12 months or history of malignant obstruction requiring a bilary stent, unless stably treated with no prior obstruction or blockage of the stent.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study-drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, make the subject inappropriate for this study.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CHIR-258 (TKI258)
Drug: CHIR-258 (TKI258)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
dose limiting toxicity (DLT) to define the maximum tolerated dose (MTD). The DLT is defined as treatment related grade 3 or grade 4 adverse events or abnormal lab test that occurred in the first 28 days after start of study drug.
Time Frame: continuous monitoring for the first 28 days after start of the study medication
continuous monitoring for the first 28 days after start of the study medication

Secondary Outcome Measures

Outcome Measure
Time Frame
characterize pharmacokinetic (PK) profile of study drug after single and repeated doses. The PK profile includes maximum blood concentration (Cmax) and time to reach maximum blood concentration (Tmax).
Time Frame: day 1 and day 15 at the following timepoints: pre-drug and 30 minutes, 1, 2, 3, 4, 5, 6, and 8 hours after dose
day 1 and day 15 at the following timepoints: pre-drug and 30 minutes, 1, 2, 3, 4, 5, 6, and 8 hours after dose
Pharmacodynamics (PD) in terms of serine-threonine kinase phosphorylation inhibition in blood before and after dose
Time Frame: day 1 and day 15 at the following timepoints: pre-drug, 4 and 24 hours after dose
day 1 and day 15 at the following timepoints: pre-drug, 4 and 24 hours after dose
Antitumor activity by comparing baseline and post-treatment changes. Tumor assessment will be performed using the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: baseline and once every two months thereafter
baseline and once every two months thereafter
urinary metabolic profiling - examination of the ratio of beta-hydroxycortisol/cortisol
Time Frame: 24 hour urine collection on day 1
24 hour urine collection on day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Collaborators

Chiron Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

October 1, 2006

Study Registration Dates

First Submitted

December 2, 2010

First Submitted That Met QC Criteria

January 4, 2011

First Posted (Estimate)

January 5, 2011

Study Record Updates

Last Update Posted (Estimate)

January 5, 2011

Last Update Submitted That Met QC Criteria

January 4, 2011

Last Verified

January 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTKI258A2101 (CHIR-258-001)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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