Clinical trial NCT00247676: An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer
Official title: An Open Label International Multi-Center Phase 2 Activity And Safety Study Of SU011248 In Patients With Unresectable Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Neoplasms
Unresectable Hepatocellular Carcinoma
Keywords: Liver neoplasms, sunitinib, Phase 2
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-11-02
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Best Overall Response
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
measure: Objective Response (CR or PR)
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
Secondary outcomes:
measure: Duration of Objective Response (CR or PR)
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer
measure: Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)
timeFrame: 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
measure: Best Overall Response of PR or SD With Duration ≥12 Weeks
timeFrame: 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
measure: Progression-Free Survival (Overall ITT)
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death
measure: Progression-Free Survival (ITT Child Pugh Class A Subject Population)
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death
measure: Time to Tumor Progression (Overall ITT)
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
measure: Time to Tumor Progression (ITT Child Pugh Class A Subject Population)
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
measure: Overall Survival (Overall ITT)
timeFrame: From start of study treatment until death.
measure: Overall Survival (ITT Child Pugh Class A Subject Population)
timeFrame: From start of study treatment until death.
measure: 1-Year Survival Probability
timeFrame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year.
measure: Trough Plasma Concentrations (Ctrough) of Sunitinib
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)
measure: Ctrough of SU-012662 (Metabolite of Sunitinib)
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)
measure: Ctrough of Total Drug (Sunitinib + SU-012662)
timeFrame: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)
measure: Dose-Corrected Ctrough of Sunitinib
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)
measure: Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)
measure: Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
timeFrame: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)
measure: Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs)
timeFrame: Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1)
measure: Tissue Tumor Markers Assessed by Tumor Biopsy
timeFrame: Day 28 of Cycle 1 (optional)
measure: Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)
measure: Plasma Concentration of VEGF-C
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)
measure: Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)
measure: Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)
measure: Plasma Concentration of Soluble KIT (sKIT)
timeFrame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)
Other outcomes:
Locations:
city: Clichy Cedex
country: France
facility: Pfizer Investigational Site
city: Rennes Cedex
country: France
facility: Pfizer Investigational Site
city: Saint Herrblain Cedex
country: France
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Taipei
country: Taiwan
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Harmon CS, DePrimo SE, Raymond E, Cheng AL, Boucher E, Douillard JY, Lim HY, Kim JS, Lechuga MJ, Lanzalone S, Lin X, Faivre S. Mechanism-related circulating proteins as biomarkers for clinical outcome in patients with unresectable hepatocellular carcinoma receiving sunitinib. J Transl Med. 2011 Jul 25;9:120. doi: 10.1186/1479-5876-9-120.
citation: Faivre S, Zappa M, Vilgrain V, Boucher E, Douillard JY, Lim HY, Kim JS, Im SA, Kang YK, Bouattour M, Dokmak S, Dreyer C, Sablin MP, Serrate C, Cheng AL, Lanzalone S, Lin X, Lechuga MJ, Raymond E. Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. Clin Cancer Res. 2011 Jul 1;17(13):4504-12. doi: 10.1158/1078-0432.CCR-10-1708. Epub 2011 Apr 29.
citation: Faivre S, Raymond E, Boucher E, Douillard J, Lim HY, Kim JS, Zappa M, Lanzalone S, Lin X, Deprimo S, Harmon C, Ruiz-Garcia A, Lechuga MJ, Cheng AL. Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study. Lancet Oncol. 2009 Aug;10(8):794-800. doi: 10.1016/S1470-2045(09)70171-8. Epub 2009 Jul 6.