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An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer

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ClinicalTrials.gov Identifier: NCT00247676
Recruitment Status : Completed
First Posted : November 2, 2005
Results First Posted : February 2, 2010
Last Update Posted : February 18, 2010
Sponsor:
Information provided by:
Pfizer

Tracking Information
First Submitted Date  ICMJE November 1, 2005
First Posted Date  ICMJE November 2, 2005
Results First Submitted Date  ICMJE January 6, 2010
Results First Posted Date  ICMJE February 2, 2010
Last Update Posted Date February 18, 2010
Study Start Date  ICMJE February 2006
Actual Primary Completion Date February 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2010)
  • Best Overall Response [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter ]
    Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
  • Objective Response (CR or PR) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter ]
    Number of patients with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in patients with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.
Original Primary Outcome Measures  ICMJE
 (submitted: November 1, 2005)
Overall confirmed objective response rate
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2010)
  • Duration of Objective Response (CR or PR) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer ]
    Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions.
  • Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks on study ]
    Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR, or SD for at least 12 weeks on study according to RECIST. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
  • Best Overall Response of PR or SD With Duration ≥12 Weeks [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks or death due to cancer ]
    Number of patients with best overall response of PR or SD with duration ≥ 12 weeks. Best overall response was defined as the time from the first documentation of tumor response that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
  • Progression-Free Survival (Overall ITT) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death ]
    Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.
  • Progression-Free Survival (ITT Child Pugh Class A Subject Population) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death ]
    Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.
  • Time to Tumor Progression (Overall ITT) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter ]
    Time from the start of study treatment to the first documentation of objective tumor progression.
  • Time to Tumor Progression (ITT Child Pugh Class A Subject Population) [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter ]
    Time from the start of study treatment to the first documentation of objective tumor progression.
  • Overall Survival (Overall ITT) [ Time Frame: From start of study treatment until death. ]
    Time from the date of first dose of study medication to the date of death due to any cause.
  • Overall Survival (ITT Child Pugh Class A Subject Population) [ Time Frame: From start of study treatment until death. ]
    Time from the date of first dose of study medication to the date of death due to any cause.
  • 1-Year Survival Probability [ Time Frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year. ]
    Probability of survival 1 year after the first dose of study treatment.
  • Trough Plasma Concentrations (Ctrough) of Sunitinib [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) ]
    Ctrough = the concentration prior to study drug administration.
  • Ctrough of SU-012662 (Metabolite of Sunitinib) [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) ]
    Ctrough = the concentration prior to study drug administration.
  • Ctrough of Total Drug (Sunitinib + SU-012662) [ Time Frame: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) ]
    Ctrough = the concentration prior to study drug administration.
  • Dose-Corrected Ctrough of Sunitinib [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) ]
    Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]).
  • Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib) [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) ]
    Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]).
  • Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662) [ Time Frame: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) ]
    Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]).
  • Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs) [ Time Frame: Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1) ]
    Blood samples for the assessment of CECs and circulating CEPs were planned to be obtained for subjects in Part 1 of the study, and for a subset of subjects in Part 2 of the study to complete the angiogenic profile of unresectable hepatocellular carcinoma, in addition to the soluble protein evaluation.
  • Tissue Tumor Markers Assessed by Tumor Biopsy [ Time Frame: Day 28 of Cycle 1 (optional) ]
    Provision of previously collected tumor paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block) for correlative laboratory analysis was optional. For all subjects showing OR on study, it was highly recommended to provide previously collected paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block). These samples were to be analyzed for markers that may be associated with tumor proliferation or angiogenesis.
  • Plasma Concentration of Vascular Endothelial Growth Factor (VEGF) [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) ]
    Plasma concentrations of VEGF that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by e nzyme-linked immunosorbent assay (ELISA). Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
  • Plasma Concentration of VEGF-C [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) ]
    Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
  • Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2) [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) ]
    Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline). Samples below the limit of quantitation and samples with insufficient volume available were excluded.
  • Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) ]
    Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
  • Plasma Concentration of Soluble KIT (sKIT) [ Time Frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) ]
    Plasma concentrations of sKIT that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2005)
Clinical Benefit Rate, Duration of Response, Progression-free survival; Time to progression; Overall survival; Probability of survival at 1 year, safety, pk, biomarkers
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer
Official Title  ICMJE An Open Label International Multi-Center Phase 2 Activity And Safety Study Of SU011248 In Patients With Unresectable Hepatocellular Carcinoma
Brief Summary The study will consist of two parts. In Part 1 the study will start enrolling 38 patients and then further 25 patients up to a total of 63 eligible patients. If the study gives good results it can be expanded to a total of 160 patients. SU011248 will be administered orally daily for 4 weeks followed by a 2-week rest at a starting dose of 50 mg [milligrams] with provision for dose reduction based on tolerability. All patients will receive repeated cycles of SU011248 until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Liver Neoplasms
  • Unresectable Hepatocellular Carcinoma
Intervention  ICMJE Drug: Sunitinib (SU011248)
Sunitinib 50 mg by oral capsule, daily for 4 weeks in every 6 week cycle until progression or unacceptable toxicity.
Other Name: SU011248, Sutent
Study Arms  ICMJE Experimental: A
Intervention: Drug: Sunitinib (SU011248)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 3, 2009)
37
Original Enrollment  ICMJE
 (submitted: November 1, 2005)
160
Actual Study Completion Date  ICMJE February 2009
Actual Primary Completion Date February 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed diagnosis of hepatocellular carcinoma
  • Patients must present with disease not amenable to curative surgery (i.e. either hepatectomy, or liver transplant).
  • Evidence of measurable disease by radiographic technique
  • Adequate organ function.

Exclusion Criteria:

  • Prior treatment with any systemic treatment for liver cancer
  • Presence of clinically relevant ascites
  • Severe hemorrhage <4 weeks of starting study treatment.
  • Diagnosis of second malignancy within last 3 years
  • History of or known brain metastases, spinal cord compression, or carcinomatous meningitis
  • Known human immunodeficiency virus (HIV)
  • Serious acute or chronic illness
  • Current treatment on another clinical trial
  • Pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Korea, Republic of,   Taiwan
Removed Location Countries Greece,   Hong Kong
 
Administrative Information
NCT Number  ICMJE NCT00247676
Other Study ID Numbers  ICMJE A6181055
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Director, Clinical Trial Disclosure Group, Pfizer Inc
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP