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

NCT00715182 | Completed Phase 1

• 2 other identifiers: CTKI258A21072007-004391-39
• Study Type: interventional
• Target: 87
• Locations: 6 countries
• Sites: 12

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 diagnosed with advanced or metastatic renal cell cancer that is refractory to standard therapy or for which no curative standard therapy exists.

Conditions

Advanced/ Metastatic Renal Cell Cancer

Keywords

Renal Cell Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: To determine the MTD of TKI258, administered orally on a 5 days on/2 days off schedule to adult patients with advanced or metastatic RCC whose diseases have progressed despite standard therapy or for whom no standard anticancer therapy exists.

  at end of phase I

• Phase II: To determine anti-tumor activity of TKI258 in advanced or metastatic RCC patients with predominant clear cell histology that have been previously treated with VEGF receptor tyrosine kinase inhibitor (sunitinib and/or sorafenib).

  at end of phase II

Secondary Outcomes (5)

• To assess the safety profile of TKI258

  cycle 1: day 1,8,15,26; cycle 2: day 15, 28; cycle 3+: day 28 & at end of study

• To assess the effect of TKI258 on plasma biomarkers, pre- and post-treatment

  cycle 1: day 1,15,26; cycle 2: 15 & 28; every other cycles: day 28 & at end of study

• To explore the pharmacokinetic and pharmacodynamic relationship

  end of study

• To characterize the single and multiple-dose PK profiles of oral TKI258

  cycle 1: day 1, 8, 15 &26; cycle 2 & 3: day 15 & 28

• Progression free survival and over all survival

  end of study

Study Arms (1)

TKI258

EXPERIMENTAL

Drug: TKI258

Interventions

TKI258 DRUG

TKI258

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

San Francisco, California, United States

Location

Novartis Investigative Site

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

Seattle, Washington, 98109-1023, United States

Location

Novartis Investigative Site

Bordeaux, 33075, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Taipei, Taiwan, ROC, 112, Taiwan

Location

Novartis Investigative Site

Taichung, 40705, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Links

• Results for CTKI258A2107 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

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: July 11, 2008
• First Posted: July 15, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: December 21, 2020

Record last verified: 2013-01

Locations

US (3); TW (3); DE (2); NL (1); FR (2); ES (1)