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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sunitinib (SU011248) | Drug | Sunitinib 50 mg by oral capsule, daily for 4 weeks in every 6 week cycle until progression or unacceptable toxicity. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response | 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. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
| Objective Response (CR or PR) | 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. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Objective Response (CR or PR) | 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. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Clichy | 92118 | France | |||
| Pfizer Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21787417 | Derived | 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. | |
| 21531821 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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This study was designed using a Simon 2-stage design with the objective response rate as the primary efficacy endpoint. Enrollment was halted after the first stage because the minimum number of responders by Response Evaluation Criteria in Solid Tumors (RECIST) needed to continue into Stage 2 was not reached.
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| ID | Title | Description |
|---|---|---|
| FG000 | 50 Milligram (mg) Sunitinib | Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 50 Milligram (mg) Sunitinib | Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Duration of Objective Response (CR or PR) | 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. | From the Overall ITT population, only 1 subject had Objective Response for evaluation of duration of objective response. | Posted | Number | Weeks | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 50 Milligram (mg) Sunitinib | Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (v11.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (v11.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc | 1-800-718-1021 | ClinicalTrials.govCallCenter@pfizer.com |
| ID | Term |
|---|---|
| D008113 | Liver Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000077210 | Sunitinib |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks) | 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. | 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 |
| Best Overall Response of PR or SD With Duration ≥12 Weeks | 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. | 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 |
| Progression-Free Survival (Overall ITT) | Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death |
| Progression-Free Survival (ITT Child Pugh Class A Subject Population) | Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death |
| Time to Tumor Progression (Overall ITT) | Time from the start of study treatment to the first documentation of objective tumor progression. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
| Time to Tumor Progression (ITT Child Pugh Class A Subject Population) | Time from the start of study treatment to the first documentation of objective tumor progression. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
| Overall Survival (Overall ITT) | Time from the date of first dose of study medication to the date of death due to any cause. | From start of study treatment until death. |
| Overall Survival (ITT Child Pugh Class A Subject Population) | Time from the date of first dose of study medication to the date of death due to any cause. | From start of study treatment until death. |
| 1-Year Survival Probability | Probability of survival 1 year after the first dose of study treatment. | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year. |
| Trough Plasma Concentrations (Ctrough) of Sunitinib | Ctrough = the concentration prior to study drug administration. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
| Ctrough of SU-012662 (Metabolite of Sunitinib) | Ctrough = the concentration prior to study drug administration. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
| Ctrough of Total Drug (Sunitinib + SU-012662) | Ctrough = the concentration prior to study drug administration. | Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
| Dose-Corrected Ctrough of Sunitinib | Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]). | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
| Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib) | Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]). | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
| Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662) | Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]). | Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
| Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs) | 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. | Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1) |
| Tissue Tumor Markers Assessed by Tumor Biopsy | 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. | Day 28 of Cycle 1 (optional) |
| Plasma Concentration of Vascular Endothelial Growth Factor (VEGF) | 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. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
| Plasma Concentration of VEGF-C | 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. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
| Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2) | 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. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
| Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | 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. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
| Plasma Concentration of Soluble KIT (sKIT) | 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. | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
| Rennes |
| 4422935062 |
| France |
| Pfizer Investigational Site | Saint Herrblain Cedex | 44805 | France |
| Pfizer Investigational Site | Seoul | 110-744 | South Korea |
| Pfizer Investigational Site | Seoul | 135-710 | South Korea |
| Pfizer Investigational Site | Seoul | 138-736 | South Korea |
| Pfizer Investigational Site | Seoul | 152-703 | South Korea |
| Pfizer Investigational Site | Taipei | 110 | Taiwan |
| 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. |
| 19586800 | Derived | 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. |
| Other |
|
| Withdrawal by Subject |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Best Overall Response | 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. | Intent-to-treat (ITT) population includes all patients enrolled in the study that received at least 1 dose of study medication. | Posted | Number | participants | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
|
|
|
| Secondary | Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks) | 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. | ITT | Posted | Number | participants | 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 |
|
|
|
|
| Secondary | Best Overall Response of PR or SD With Duration ≥12 Weeks | 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. | ITT | Posted | Number | participants | 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 |
|
|
|
| Secondary | Progression-Free Survival (Overall ITT) | Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause. | ITT | Posted | Median | 95% Confidence Interval | Weeks | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death |
|
|
|
| Secondary | Progression-Free Survival (ITT Child Pugh Class A Subject Population) | Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause. | ITT Child Pugh Class A (assessment of liver function) subject population = subjects enrolled in the study with Child-Pugh Class A that received at least 1 dose of study medication. | Posted | Median | 95% Confidence Interval | Weeks | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death |
|
|
|
| Secondary | Time to Tumor Progression (Overall ITT) | Time from the start of study treatment to the first documentation of objective tumor progression. | ITT | Posted | Median | 95% Confidence Interval | Weeks | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
|
|
|
| Primary | Objective Response (CR or PR) | 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. | ITT | Posted | Number | participants | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
|
|
|
|
| Secondary | Time to Tumor Progression (ITT Child Pugh Class A Subject Population) | Time from the start of study treatment to the first documentation of objective tumor progression. | ITT Child Pugh Class A (assessment of liver function) subject population | Posted | Median | 95% Confidence Interval | Weeks | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter |
|
|
|
| Secondary | Overall Survival (Overall ITT) | Time from the date of first dose of study medication to the date of death due to any cause. | ITT | Posted | Median | 95% Confidence Interval | Weeks | From start of study treatment until death. |
|
|
|
| Secondary | Overall Survival (ITT Child Pugh Class A Subject Population) | Time from the date of first dose of study medication to the date of death due to any cause. | ITT Child Pugh Class A (assessment of liver function) subject population | Posted | Median | 95% Confidence Interval | Weeks | From start of study treatment until death. |
|
|
|
| Secondary | 1-Year Survival Probability | Probability of survival 1 year after the first dose of study treatment. | ITT | Posted | Number | Probability | From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year. |
|
|
|
|
| Secondary | Trough Plasma Concentrations (Ctrough) of Sunitinib | Ctrough = the concentration prior to study drug administration. | Pharmacokinetic (PK) = All subjects enrolled in the study who at least 1 PK sample collected. | Posted | Mean | Standard Deviation | nanograms (ng)/milliliter (mL) | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Ctrough of SU-012662 (Metabolite of Sunitinib) | Ctrough = the concentration prior to study drug administration. | PK | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Ctrough of Total Drug (Sunitinib + SU-012662) | Ctrough = the concentration prior to study drug administration. | PK | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Dose-Corrected Ctrough of Sunitinib | Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]). | PK | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib) | Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]). | PK | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662) | Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x [starting dose/actual dose]). | PK | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs) | 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. | ITT. Blood samples for CECs and CEP cells were collected during the study, but evaluations of these samples were not performed. | Posted | Mean | Standard Deviation | cells/mL | Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1) |
|
|
| Secondary | Tissue Tumor Markers Assessed by Tumor Biopsy | 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. | ITT. Tumor biopsy results were collected optionally in 5 subjects; however, no evaluations were performed. | Posted | Mean | Standard Deviation | intensity score | Day 28 of Cycle 1 (optional) |
|
|
| Secondary | Plasma Concentration of Vascular Endothelial Growth Factor (VEGF) | 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. | ITT | Posted | Median | Full Range | picograms (pg)/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Plasma Concentration of VEGF-C | 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. | ITT | Posted | Median | Full Range | pg/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2) | 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. | ITT | Posted | Median | Full Range | pg/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | 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. | ITT | Posted | Median | Full Range | pg/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| Secondary | Plasma Concentration of Soluble KIT (sKIT) | 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. | ITT | Posted | Median | Full Range | pg/mL | Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28) |
|
|
|
| 24 |
| 37 |
| 37 |
| 37 |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA (12.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Peritoneal effusion | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Peritoneal haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypothermia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hepatic cirrhosis | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Empyema | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypercreatinaemia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Coma | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nervous system disorder | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neurological decompensation | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA (12.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (12.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Gingivitis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Varices oesophageal | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pitting oedema | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Blood bilirubin | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Haemoglobin | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Platelet count | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| White blood cell count | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (12.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Ageusia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Periorbital oedema | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of <60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), <12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
| D008107 |
| Liver Diseases |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Title | Measurements |
|---|
|
| Progressive Disease |
|
| Not Evaluable |
|
| Missing |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 3, Day 1 (n=16) |
|
| Cycle 3, Day 28 (n=16) |
|
| Cycle 5, Day 28 (n=12) |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 3, Day 1 (n=16) |
|
| Cycle 3, Day 28 (n=16) |
|
| Cycle 5, Day 28 (n=12) |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 3, Day 1 (n=8) |
|
| Cycle 3, Day 28 (n=16) |
|
| Cycle 5, Day 28 (n=11) |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 1 (n=11) |
|
| Cycle 2, Day 28 (n=15) |
|
| Cycle 3, Day 1 (n=6) |
|
| Cycle 3, Day 28 (n=10) |
|
| Cycle 5, Day 28 (n=10) |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 1 (n=12) |
|
| Cycle 2, Day 28 (n=15) |
|
| Cycle 3, Day 1 (n=7) |
|
| Cycle 3, Day 28 (n=10) |
|
| Cycle 5, Day 28 (n=10) |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 28 (n=15) |
|
| Cycle 3, Day 1 (n=8) |
|
| Cycle 3, Day 28 (n=10) |
|
| Cycle 5, Day 28 (n=10) |
|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 5, Day 28 (n=12) |
|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 5, Day 28 (n=12) |
|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 5, Day 28 (n=12) |
|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 5, Day 28 (n=12) |
|
|
| Cycle 2, Day 1 (n=25) |
|
| Cycle 2, Day 28 (n=19) |
|
| Cycle 5, Day 28 (n=12) |
|