Status:

COMPLETED

A Phase I/II Study to Assess the Safety and Efficacy of TKI258 for the Treatment of Refractory Advanced/Metastatic Renal Cell Cancer

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Advanced/ Metastatic Renal Cell Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

This is a phase I/II open-label study to delineate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of TKI258. The eligible subject population consists of subjects who have been d...

Eligibility Criteria

Inclusion

  • For phase I, confirmed advanced/ metastatic renal cell carcinoma for which no other therapeutic options exist.
  • For phase II, must have been previously treated with VEGF receptor tyrosine kinase inhibitor (sunitinib and/or sorafenib).
  • For phase II, must have at least one measurable lesion at baseline.
  • For both phase I \& II, measurable histologically or cytology confirmed progressive metastatic renal cell carcinoma with predominant clear cell histology (\>50%).
  • At least 4 weeks must have elapsed since any prior anti-cancer therapy (6 weeks for nitrosoureas or mitomycin C).
  • Must have recovered from adverse events (to grade 1 or less toxicity according to CTCAE 3.0) due to agents administered more than 28 days earlier.
  • Must be eighteen years of age or older
  • ECOG performance status 0 or 1.
  • Must meet baseline laboratory requirement
  • Life expectancy greater than or equal to 12 weeks.
  • Signed and witnessed informed consent prior to any screening procedures.

Exclusion

  • Concurrent therapy with any other investigational agent within 28 days prior to baseline.
  • Pregnant or breast feeding women.
  • Clinically significant cardiac disease (New York Heart Association, Class III or IV) or impaired cardiac function or clinically significant cardiac diseases.
  • Uncontrolled infection.
  • Diabetes mellitus with signs of clinically significant peripheral vascular disease.
  • Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month.
  • Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, adrenal or thyroid glands.
  • Prior acute or chronic pancreatitis of any etiology.
  • Acute and chronic liver disease and all chronic liver impairment.
  • Malabsorption syndrome or uncontrolled gastrointestinal symptoms (such as nausea, diarrhea and vomiting) with toxicity greater than NCI CTCAE grade 2.
  • Other severe, acutem or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and, in the judgement of the investigator, would make the subject inappropriate for this study.
  • Treatment with any of the medications that have a potential risk of prolonging the QT interval or inducing Torsades de Points and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • Use of ketoconazole, erythromycin, carbamazapine, phenobarbital, rifampin, phenytoin and quinidine 2 weeks prior to baseline.
  • Major surgery within 28 days prior to starting study drug or who have not recovered from side effects of such therapy.
  • Known diagnosis of HIV infection (HIV testing is not mandatory).
  • History of another clinically significant primary malignancy that requires active intervention.
  • Patients with brain metastases as assessed by radiologic imaging.
  • Alcohol or substance abuse disorder.

Key Trial Info

Start Date :

July 1 2008

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

July 1 2012

Estimated Enrollment :

87 Patients enrolled

Trial Details

Trial ID

NCT00715182

Start Date

July 1 2008

End Date

July 1 2012

Last Update

December 21 2020

Active Locations (12)

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Page 1 of 3 (12 locations)

1

Novartis Investigative Site

San Francisco, California, United States

2

Novartis Investigative Site

Durham, North Carolina, United States, 27710

3

Novartis Investigative Site

Seattle, Washington, United States, 98109-1023

4

Novartis Investigative Site

Bordeaux, France, 33075