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

Phase 1
18 Years
Not Enrolling
Neoplasms, Cancer, Tumors

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Trial Information

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

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

- 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

Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

continuous monitoring for the first 28 days after start of the study medication

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

CTKI258A2101 (CHIR-258-001)



Start Date:

December 2003

Completion Date:

Related Keywords:

  • Neoplasms
  • Cancer
  • Tumors
  • Neoplasms
  • Cancer
  • Tumors
  • Administration
  • oral
  • CHIR258
  • CHIR-258
  • CHIR 258
  • TKI258
  • TKI-258
  • TKI 258
  • dose finding
  • Neoplasms