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This study determined the maximum tolerated dose and safety of SU011248 (sunitinib malate, SUTENT) in combination with FOLFOX [Leucovorin + Fluorouracil (5-FU) + Oxaliplatin]. Three different dosing regimens with starting doses of sunitinib at 37.5 mg/day (Schedule 2/2, Schedule 4/2, and Continuous Dosing) were tested in patients with advanced solid tumors, including colorectal cancer.
Study Design: Treatment, Single Group Assignment (7 cohorts), Open Label, Non-Randomized, Safety Study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm | Experimental | SU011248 [sunitinib] in combination with FOLFOX; FOLFOX is a chemotherapy regimen that combines oxaliplatin and leucovorin with bolus and infusion 5-FU. The modified FOLFOX 6 (mFOLFOX6) regimen is one of several different regimens of FOLFOX used in clinic, according to different dosages of the 4 drugs. mFOLFOX6 was administered every 2 weeks on Days 1 and 2 of each cycle. 25, 37.5 and 50 mg/day, oral, administered on an outpatient basis in three different dosing regimens: schedule 2/2 (2 weeks on, 2 weeks off), schedule 4/2 (4 weeks on, 2 weeks off), and continuous daily dosing (every day); FOLFOX will be administered every 2 weeks, using the modified FOLFOX 6 (mFOLFOX6) regimen, consisting of: oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 as a 2-hr IV infusion; 5-FU 400 mg/m2 IV bolus, followed by - 5-FU 2400 mg/m2 as a 46-hr IV infusion |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sunitinib + FOLFOX | Drug | 37.5 mg sunitinib + modified FOLFOX6 (Schedule 2/2) |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported. | up to 20 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response (OR) | From the start of treatment until disease progression/recurrence. OR=confirmed Complete Response (CR) or confirmed Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR = disappearance of all target lesions. CR was confirmed if it persisted on repeat imaging study ≥ 4 weeks after initial documentation of response. PR = ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PR was confirmed if it persisted on repeat imaging study ≥ 4 weeks after initial documentation of response. |
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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 | Aurora | Colorado | 80045 | United States | ||
| Pfizer Investigational Site |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) | Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| FG001 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) | Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| FG002 | 50 mg Sunitinib + Modified FOLFOX6 (CRC Only, Schedule 2/2) | CRC = colorectal cancer. Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| FG003 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 |
| FG004 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 |
| FG005 | 37.5 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. |
| FG006 | 25 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) | Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| BG001 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported. | Intent to treat (ITT) = all subjects enrolled in the study that received at least one dose of study medication. Subjects who did not complete the follow-up period for dose limiting toxicity assessment because of death from progressive disease or other non-treatment related events were replaced. | Posted | Number | participants | up to 20 weeks |
|
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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 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) | Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (12.0) | 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 |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000077210 | Sunitinib |
| C410216 | Folfox protocol |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| sunitinib + FOLFOX | Drug | 50 mg sunitinib + modified FOLFOX6 (Schedule 2/2) |
|
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| sunitinib + FOLFOX | Drug | 50 mg sunitinib + modified FOLFOX6 ( CRC, only Schedule 2/2) |
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| sunitinib + FOLFOX | Drug | 37.5 mg sunitinib + modified FOLFOX6 (Schedule 4/2) |
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| sunitinib + FOLFOX | Drug | 50 mg sunitinib + modified FOLFOX6 (Schedule 4/2) |
|
|
| sunitinib + FOLFOX | Drug | 37.5 mg sunitinib + modified FOLFOX6 (Continuous Dosing) |
|
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| sunitinib + FOLFOX | Drug | 25 mg sunitinib + modified FOLFOX6 (Continuous Dosing) |
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| From start of treatment until Day 8 of Cycles 4 and 8 (2/2 Schedule), Day 8 of Cycles 3 and 6 (4/2 Schedule), and Day 1 of Cycles 3 and 7 (Continuous Dosing) |
| Maximum Plasma Concentration (Cmax) of Sunitinib | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Time to Cmax (Tmax) of Sunitinib | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Minimum Plasma Concentration (Cmin) of Sunitinib | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Clearance (CL/F) of Sunitinib | Drug clearance (CL/F) = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours. | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib | AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method. | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Terminal Phase Half-Life (t1/2) of Sunitinib | t1/2 = terminal phase half-life. t1/2 was obtained by natural log of 2 (ln2) divided by the rate constant for terminal phase (kel). | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Cmax of SU-012662 (Sunitinib's Metabolite) | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Tmax of SU-012662 (Sunitinib's Metabolite) | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Cmin of SU-012662 (Sunitinib's Metabolite) | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| AUC24 for SU-012662 (Sunitinib's Metabolite) | AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method. | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose. |
| CL/F of SU-012662 (Sunitinib's Metabolite) | CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours. | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| T1/2 of SU-012662 (Sunitinib's Metabolite) | t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Cmax of Free Platinum | Oxaliplatin was metabolized to platinum and free platinum was measured. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Tmax of Free Platinum | Oxaliplatin was metabolized to platinum and free platinum was measured. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum | Oxaliplatin was metabolized to platinum and free platinum was measured. AUCinf = Area under the plasma concentration-time profile from time zero (pre-dose) to infinity. AUCinf was obtained by the Linear/Log trapezoidal method. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| T1/2 for Free Platinum | t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free platinum was measured. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Cmax of Total Platinum | Oxaliplatin was metabolized to platinum and total platinum was measured. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Tmax of Total Platinum | Oxaliplatin was metabolized to platinum and total platinum was measured. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum | Oxaliplatin was metabolized to platinum and total platinum was measured. AUC48 = Area under the plasma concentration-time profile from time zero (pre-dose) to forty-eight hours. AUC48 was obtained by the Linear/Log trapezoidal method. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Steady State Concentration (Css) of Fluorouracil (5-FU) | Steady state is reached when the amount of drug getting into the system per unit time is equal to the amount of drug cleared from the system. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Steady State Clearance (CLss) of 5-FU | CLss was determined by total amount of drug received during infusion or duration of infusion (Ki) divided by Css. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Area Under the Curve (AUC) of 5-FU | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Cmax of 5-FU | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| T1/2 of Free Platinum, Total Platinum, and 5-FU | t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free and total platinum were measured. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| CL/F of Free Platinum, Total Platinum, and 5-FU | CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours. | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
| Cmin of Free Platinum, Total Platinum, and 5-FU | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
| Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) | Volume endothelial Ktrans was estimated by fitting the tissue contrast agent time course to the Kety equation (Tofts model for analysis of DCE-MRI data). | Cycle 3 (Day 1), Cycle 3 (Day 8) |
| Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI | IAUC: The initial area under the curve was estimated by integrating the area under the contrast agent concentration time course for the first 90 seconds after bolus arrival in the tumor. | Cycle 3 (Day 1) and Cycle 3 (Day 8) |
| Nashville |
| Tennessee |
| 37232 |
| United States |
| Pfizer Investigational Site | Dallas | Texas | 75246 | United States |
| Adverse Event |
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| Death |
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| Protocol Violation |
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| Withdrawal by Subject |
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| Other |
|
Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| BG002 | 50 mg Sunitinib + Modified FOLFOX6 (CRC Only, Schedule 2/2) | CRC = colorectal cancer. Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| BG003 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 |
| BG004 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 |
| BG005 | 37.5 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. |
| BG006 | 25 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. |
| BG007 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| 50 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) |
Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| OG002 | 50 mg Sunitinib + Modified FOLFOX6 (CRC Only, Schedule 2/2) | CRC = colorectal cancer. Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. |
| OG003 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 |
| OG004 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 |
| OG005 | 37.5 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. |
| OG006 | 25 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. |
|
|
| Secondary | Objective Response (OR) | From the start of treatment until disease progression/recurrence. OR=confirmed Complete Response (CR) or confirmed Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR = disappearance of all target lesions. CR was confirmed if it persisted on repeat imaging study ≥ 4 weeks after initial documentation of response. PR = ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PR was confirmed if it persisted on repeat imaging study ≥ 4 weeks after initial documentation of response. | ITT | Posted | Number | participants | From start of treatment until Day 8 of Cycles 4 and 8 (2/2 Schedule), Day 8 of Cycles 3 and 6 (4/2 Schedule), and Day 1 of Cycles 3 and 7 (Continuous Dosing) |
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| Secondary | Maximum Plasma Concentration (Cmax) of Sunitinib | ITT population of subjects who had completed pharmacokinetic (PK) blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Time to Cmax (Tmax) of Sunitinib | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Median | Full Range | hours | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Minimum Plasma Concentration (Cmin) of Sunitinib | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Clearance (CL/F) of Sunitinib | Drug clearance (CL/F) = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | L/hr | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib | AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng*hr/mL | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Terminal Phase Half-Life (t1/2) of Sunitinib | t1/2 = terminal phase half-life. t1/2 was obtained by natural log of 2 (ln2) divided by the rate constant for terminal phase (kel). | T1/2 for sunitinib was not calculated due to short observation time. | Posted | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Cmax of SU-012662 (Sunitinib's Metabolite) | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Tmax of SU-012662 (Sunitinib's Metabolite) | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Median | Full Range | hours | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | Cmin of SU-012662 (Sunitinib's Metabolite) | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
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| Secondary | AUC24 for SU-012662 (Sunitinib's Metabolite) | AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng*hr/mL | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose. |
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| Secondary | CL/F of SU-012662 (Sunitinib's Metabolite) | CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours. | CL/F was not calculated for SU-012662. | Posted | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
|
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| Secondary | T1/2 of SU-012662 (Sunitinib's Metabolite) | t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. | T1/2 for SU-012662 was not calculated due to short observation time. | Posted | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
|
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| Secondary | Cmax of Free Platinum | Oxaliplatin was metabolized to platinum and free platinum was measured. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
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| Secondary | Tmax of Free Platinum | Oxaliplatin was metabolized to platinum and free platinum was measured. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Median | Full Range | hours | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
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| Secondary | Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum | Oxaliplatin was metabolized to platinum and free platinum was measured. AUCinf = Area under the plasma concentration-time profile from time zero (pre-dose) to infinity. AUCinf was obtained by the Linear/Log trapezoidal method. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng*hr/mL | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
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| Secondary | T1/2 for Free Platinum | t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free platinum was measured. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | hours | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
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| Secondary | Cmax of Total Platinum | Oxaliplatin was metabolized to platinum and total platinum was measured. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
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|
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| Secondary | Tmax of Total Platinum | Oxaliplatin was metabolized to platinum and total platinum was measured. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Median | Full Range | hours | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
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| Secondary | Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum | Oxaliplatin was metabolized to platinum and total platinum was measured. AUC48 = Area under the plasma concentration-time profile from time zero (pre-dose) to forty-eight hours. AUC48 was obtained by the Linear/Log trapezoidal method. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng*hr/mL | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
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|
|
| Secondary | Steady State Concentration (Css) of Fluorouracil (5-FU) | Steady state is reached when the amount of drug getting into the system per unit time is equal to the amount of drug cleared from the system. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
|
| Secondary | Steady State Clearance (CLss) of 5-FU | CLss was determined by total amount of drug received during infusion or duration of infusion (Ki) divided by Css. | ITT population of subjects who had completed PK blood sampling for at least one day. | Posted | Mean | Standard Deviation | L/hr | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
|
| Secondary | Area Under the Curve (AUC) of 5-FU | AUC for 5-FU was not calculated. | Posted | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
| Secondary | Cmax of 5-FU | Cmax of 5-FU was not calculated. | Posted | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
| Secondary | T1/2 of Free Platinum, Total Platinum, and 5-FU | t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free and total platinum were measured. | T1/2 was not calculated for Free Platinum, Total Platinum, and 5-FU. | Posted | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
| Secondary | CL/F of Free Platinum, Total Platinum, and 5-FU | CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours. | CL/F was not calculated for Free Platinum, Total Platinum, and 5-FU. | Posted | pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose |
|
|
| Secondary | Cmin of Free Platinum, Total Platinum, and 5-FU | Cmin was not calculated for Free Platinum, Total Platinum, and 5-FU. | Posted | pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose |
|
|
| Secondary | Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) | Volume endothelial Ktrans was estimated by fitting the tissue contrast agent time course to the Kety equation (Tofts model for analysis of DCE-MRI data). | No pharmacodynamic assessments were performed due to limited number of DCE-MRI scans collected. | Posted | Cycle 3 (Day 1), Cycle 3 (Day 8) |
|
|
| Secondary | Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI | IAUC: The initial area under the curve was estimated by integrating the area under the contrast agent concentration time course for the first 90 seconds after bolus arrival in the tumor. | No pharmacodynamic assessments were performed due to limited number of DCE-MRI scans collected. | Posted | Cycle 3 (Day 1) and Cycle 3 (Day 8) |
|
|
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 2/2) | Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. | 4 | 9 | 9 | 9 |
| EG002 | 50 mg Sunitinib + Modified FOLFOX6 (CRC Only, Schedule 2/2) | CRC = colorectal cancer. Schedule 2/2 = Sunitinib administered daily for 2 weeks followed by a 2-week off period. Sunitinib was administered during every other cycle of modified FOLFOX6. | 0 | 5 | 5 | 5 |
| EG003 | 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 | 7 | 12 | 12 | 12 |
| EG004 | 50 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) | Schedule 4/2 = Sunitinib administered daily for 4 weeks followed by a 2-week off period, overlapping with 3 cycles of modified FOLFOX6 | 3 | 9 | 9 | 9 |
| EG005 | 37.5 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. | 2 | 6 | 6 | 6 |
| EG006 | 25 mg Sunitinib + Modified FOLFOX6 (Continuous Dosing) | Continuous Dosing = Sunitinib administered daily for 16 weeks. Off periods and dosage depended on toxicities observed. Sunitinib was administered with modified FOLFOX6. | 4 | 8 | 8 | 8 |
| Febrile neutropenia | 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 |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Liver abscess | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
|
| Blood bilirubin increased | 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 |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular 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 |
|
| Vision blurred | Eye disorders | MedDRA (12.0) | Systematic Assessment |
|
| Visual impairment | Eye 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 |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Fatigue | 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 |
|
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Temperature intolerance | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (12.0) | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | 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 |
|
| Alanine aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Aspartate aminotransferase | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Blood alkaline phosphatase | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| White blood cell count decreased | 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 |
|
| Hyperglycaemia | 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 |
|
| 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 |
|
| Back 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 |
|
| 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 |
|
| Hyperaesthesia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Cough | 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 |
|
| Oropharyngeal pain | 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 |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
|
| Skin exfoliation | 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 information other than study results.
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |