Study Of CP-751,871 In Combination With Sunitinib In Patients With Advanced Solid Tumors
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT00729833
Collaborator
(none)
45
4
1
55
11.3
0.2
Study Details
Study Description
Brief Summary
The study is being conducted to determine the maximum tolerated dose, overall safety and tolerability profile, and pharmacokinetic profile of CP-751,871 and sunitinib when given in combination with advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study was closed to enrollment on 14 Jan 2011 and terminated secondary to excessive screen failure rate and for business reasons associated with Pfizer's business decision to stop development of the figitumumab compound. Safety concerns did not contribute to the decision to terminate this clinical trial.
Study Design
Study Type:
Interventional
Actual Enrollment
:
45 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1, Open Label, Sequential Cohort, Dose Escalation Study Of CP-751,871 In Combination With Sunitinib In Patients With Advanced Solid Tumors
Study Start Date
:
Sep 1, 2008
Actual Primary Completion Date
:
Aug 1, 2011
Actual Study Completion Date
:
Apr 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CP-751,871 + Sunitinib Escalating cohorts of CP-751,871 + Sunitinib |
Drug: CP-751,871
CP-751,871 IV, every 3 weeks
Drug: Sunitinib
Sunitinib - daily dosing
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-Limiting Toxicities (DLT) [Baseline up to the end of Cycle 1 (each cycle=3 weeks)]
Number of participants with treatment-related Grade 3/4 toxicities that occurred during the defined time frame or that resulted in greater than or equal to (>=) 7 days delay in administration of Cycle 2. Toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.
Secondary Outcome Measures
- Percentage of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events Grade Version 3.0 [Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose)]
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the worst CTCAE grade was reported. Severity grades were 0 (no change from normal or reference range), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), and 5 (death).
- Percentage of Participants With Hematologic Laboratory Test Abnormality [Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose)]
Percentage of participants with hematologic laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling).
- Percentage of Participants With Blood Chemistry Laboratory Test Abnormality [Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose)]
Percentage of participants with blood chemistry laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling).
- Plasma Concentration at the End of Infusion (Cendinf) of Figitumumab [0.5 hour predose and 1 hour post-infusion on Day 1 of Cycles 1 and 4]
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab [0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, 15, and 22 of Cycles 1 and 4]
AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration.
- Area Under the Curve From Time Zero to Day 22 [AUC504] of Figitumumab [0.5 hour predose and 504 hours (Day 22) post-infusion of Cycles 1 and 4]
AUC504 is the area under the plasma concentration versus time curve from time zero (predose) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.
- Plasma Decay Half-Life (t1/2) of Figitumumab [0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, and 15 of Cycles 1 and 4]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Maximum Observed Plasma Concentration (Cmax) of Sunitinib [0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib [0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1]
- Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of Sunitinib [0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1]
AUC24 is the area under the plasma concentration versus time curve from time zero (predose) to 24 hours postdose (0 to 24).
- Trough Plasma Concentration (Ctrough) of Sunitinib [0.5 hour predose on Day 1 of Cycle 2]
- Plasma Concentration at 24 Hours Postdose (C24) of Sunitinib [24 hours postdose on Day 15 of Cycle 1]
- Number of Participants With Anti-Drug Antibodies (ADA) [0.5 hour pre-infusion on Day 1 in Cycles 1 and 2, at end of treatment, and during the last scheduled follow-up visit (5 months from the last dose of study drug)]
Assays for ADA assessment specific for figitumumab would have provided information regarding an immune response to the compound.
- Number of Participants With Objective Response (OR) [Baseline, Day 15 of every 2 cycles until disease progression up to follow-up (approximately 28 days following the last dose of study drug)]
Objective response (OR) was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR was the complete disappearance of all target and non-target disease, no new lesions, or the normalization of markers (if markers were being followed). PR was greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-target disease, no new lesions, or no reappearance of lesions after a CR. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically or cytologically confirmed advanced solid tumors relapsed or refractory to standard therapy or for whom no standard therapy exists.
-
ECOG Performance Status of 0 or 1;
-
Total IGF-1 level ≥100 ng/ml;
-
ECOG Performance Status of 0 or 1
-
Adequate bone marrow, renal, and hepatic function
Exclusion Criteria:
-
Concurrent treatment with any antitumor agents with the exception of LHRH agnosits for prostate cancer patients
-
Treatment with any other investigational therapy within 4 weeks prior to study treatment
-
Major surgery within 4 weeks of study treatment
-
Prior treatment that may increase the risk of cardiac complications
-
Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or greater
-
Significant active cardiac disease, including hypertension that cannot be controlled by medications
-
Greater than three (3) prior lines of cytotoxic therapy;
-
Active infection
-
Prior IGF-IR targeted therapy;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Los Angeles | California | United States | 90095 |
| 2 | Pfizer Investigational Site | Santa Monica | California | United States | 90404 |
| 3 | Pfizer Investigational Site | Philadelphia | Pennsylvania | United States | 19111 |
| 4 | Pfizer Investigational Site | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00729833
Other Study ID Numbers:
- A4021024
First Posted:
Aug 8, 2008
Last Update Posted:
Jun 9, 2014
Last Verified:
May 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab (CP-751,871) 10 milligram/kilogram (mg/kg) intravenous (IV) on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a continuous daily dosing (CDD) schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participant experienced a dose-limiting toxicity (DLT). | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a continuous daily dosing (CDD) schedule, until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a continuous daily dosing (CDD) schedule, until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of continuous daily dosing followed by 1 week off, until disease progression or unacceptable toxicity. |
| Period Title: Overall Study | ||||
| STARTED | 20 | 7 | 12 | 6 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 20 | 7 | 12 | 6 |
Baseline Characteristics
| Arm/Group Title | Figitumumab + Sunitinib (All Combined) |
|---|---|
| Arm/Group Description | All participants who received at least one dose of figitumumab plus sunitinib. |
| Overall Participants | 45 |
| Age, Customized (participants) [Number] | |
| 18 to 44 years |
11
24.4%
|
| 45 to 64 years |
22
48.9%
|
| Greater than or equal to (>=) 65 years |
12
26.7%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
25
55.6%
|
| Male |
20
44.4%
|
Outcome Measures
| Title | Number of Participants With Dose-Limiting Toxicities (DLT) |
|---|---|
| Description | Number of participants with treatment-related Grade 3/4 toxicities that occurred during the defined time frame or that resulted in greater than or equal to (>=) 7 days delay in administration of Cycle 2. Toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. |
| Time Frame | Baseline up to the end of Cycle 1 (each cycle=3 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-Protocol Analysis Set: All participants who started treatment and who did not have first cycle major treatment deviations. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. |
| Measure Participants | 20 | 7 | 12 | 6 |
| Number [participants] |
0
0%
|
1
NaN
|
3
NaN
|
1
NaN
|
| Title | Percentage of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events Grade Version 3.0 |
|---|---|
| Description | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the worst CTCAE grade was reported. Severity grades were 0 (no change from normal or reference range), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), and 5 (death). |
| Time Frame | Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All enrolled participants who received at least 1 dose of study medication. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. |
| Measure Participants | 20 | 7 | 12 | 6 |
| Any AEs, Grade 1 |
0.0
0%
|
0.0
NaN
|
16.7
NaN
|
0.0
NaN
|
| Any AEs, Grade 2 |
20.0
44.4%
|
28.6
NaN
|
8.3
NaN
|
0.0
NaN
|
| Any AEs, Grade 3 |
40.0
88.9%
|
42.9
NaN
|
50.0
NaN
|
16.7
NaN
|
| Any AEs, Grade 4 |
10.0
22.2%
|
14.3
NaN
|
8.3
NaN
|
0.0
NaN
|
| Any AEs, Grade 5 |
30.0
66.7%
|
14.3
NaN
|
16.7
NaN
|
83.3
NaN
|
| Any AEs, Total |
100.0
222.2%
|
100.0
NaN
|
100.0
NaN
|
100.0
NaN
|
| Title | Percentage of Participants With Hematologic Laboratory Test Abnormality |
|---|---|
| Description | Percentage of participants with hematologic laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling). |
| Time Frame | Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All enrolled participants who received at least 1 dose of study medication. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. |
| Measure Participants | 20 | 7 | 12 | 6 |
| Hemoglobin |
70.0
155.6%
|
85.7
NaN
|
75.0
NaN
|
83.3
NaN
|
| Lymphocytes (Absolute) |
85.0
188.9%
|
85.7
NaN
|
91.7
NaN
|
33.3
NaN
|
| Neutrophils (Absolute) |
40.0
88.9%
|
71.4
NaN
|
16.7
NaN
|
16.7
NaN
|
| Platelets |
80.0
177.8%
|
100.0
NaN
|
58.3
NaN
|
50.0
NaN
|
| White Blood Cells |
65.0
144.4%
|
71.4
NaN
|
41.7
NaN
|
33.3
NaN
|
| Title | Percentage of Participants With Blood Chemistry Laboratory Test Abnormality |
|---|---|
| Description | Percentage of participants with blood chemistry laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling). |
| Time Frame | Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All enrolled participants who received at least 1 dose of study medication; n=number of participants evaluable for this outcome measure, respectively. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. |
| Measure Participants | 20 | 7 | 12 | 6 |
| Alanine Aminotransferase (n=19, 7, 12 ,6) |
57.9
128.7%
|
57.1
NaN
|
33.3
NaN
|
0.0
NaN
|
| Alkaline Phosphatase (n=19, 7, 12, 6) |
52.6
116.9%
|
57.1
NaN
|
58.3
NaN
|
66.7
NaN
|
| Aspartate Aminotransferase (n=19, 7, 12, 6) |
63.2
140.4%
|
71.4
NaN
|
66.7
NaN
|
16.7
NaN
|
| Bicarbonate (n=19, 7, 12, 6) |
26.3
58.4%
|
71.4
NaN
|
16.7
NaN
|
33.3
NaN
|
| Total Bilirubin (n=19, 7, 12, 6) |
21.1
46.9%
|
71.4
NaN
|
25.0
NaN
|
0.0
NaN
|
| Creatinine (n=19, 7, 12, 6) |
26.3
58.4%
|
57.1
NaN
|
41.7
NaN
|
50.0
NaN
|
| Hypercalcemia (n=19, 7, 12, 6) |
0.0
0%
|
14.3
NaN
|
16.7
NaN
|
0.0
NaN
|
| Hyperglycemia (n=19, 7, 12, 6) |
78.9
175.3%
|
100.0
NaN
|
75.0
NaN
|
83.3
NaN
|
| Hyperkalemia (n=19, 7, 12, 6) |
5.3
11.8%
|
14.3
NaN
|
16.7
NaN
|
33.3
NaN
|
| Hypermagnesemia (n=17, 7, 12, 6) |
5.9
13.1%
|
0.0
NaN
|
8.3
NaN
|
16.7
NaN
|
| Hypernatremia (n=19, 7, 12, 6) |
5.3
11.8%
|
0.0
NaN
|
0.0
NaN
|
16.7
NaN
|
| Hypoalbuminemia (n=19, 7, 12, 6) |
42.1
93.6%
|
42.9
NaN
|
33.3
NaN
|
83.3
NaN
|
| Hypocalcemia (n=19, 7, 12, 6) |
47.4
105.3%
|
57.1
NaN
|
33.3
NaN
|
50.0
NaN
|
| Hypokalemia (n=19, 7, 12, 6) |
15.8
35.1%
|
28.6
NaN
|
8.3
NaN
|
16.7
NaN
|
| Hypomagnesemia (n=17, 7, 12, 6) |
23.5
52.2%
|
71.4
NaN
|
25.0
NaN
|
33.3
NaN
|
| Hyponatremia (n=19, 7, 12, 6) |
57.9
128.7%
|
42.9
NaN
|
50.0
NaN
|
66.7
NaN
|
| Hypophosphatemia (n=17, 7, 11, 6) |
23.5
52.2%
|
57.1
NaN
|
18.2
NaN
|
0.0
NaN
|
| Title | Plasma Concentration at the End of Infusion (Cendinf) of Figitumumab |
|---|---|
| Description | |
| Time Frame | 0.5 hour predose and 1 hour post-infusion on Day 1 of Cycles 1 and 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD); n=number of participants in the indicated cycle. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 11 |
| Cycle 1 (n=11) |
203.1
(27)
|
| Cycle 4 (n=4) |
256.3
(28)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab |
|---|---|
| Description | AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration. |
| Time Frame | 0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, 15, and 22 of Cycles 1 and 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD); n=number of participants in the indicated cycle. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 8 |
| Cycle 1 (n=8) |
27320
(20)
|
| Cycle 4 (n=4) |
37850
(4)
|
| Title | Area Under the Curve From Time Zero to Day 22 [AUC504] of Figitumumab |
|---|---|
| Description | AUC504 is the area under the plasma concentration versus time curve from time zero (predose) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle. |
| Time Frame | 0.5 hour predose and 504 hours (Day 22) post-infusion of Cycles 1 and 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD); n=number of participants in the indicated cycle. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 8 |
| Cycle 1 (n=8) |
33800
(18)
|
| Cycle 4 (n=4) |
46960
(6)
|
| Title | Plasma Decay Half-Life (t1/2) of Figitumumab |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | 0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, and 15 of Cycles 1 and 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD); n=number of participants in the indicated cycle. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 8 |
| Cycle 1 (n=8) |
245.0
(55.0)
|
| Cycle 4 (n=4) |
268.0
(75.6)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Sunitinib |
|---|---|
| Description | |
| Time Frame | 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD). |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter (ng/mL)] |
39.19
(38)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib |
|---|---|
| Description | |
| Time Frame | 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD). |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 11 |
| Median (Full Range) [hours] |
4.07
|
| Title | Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of Sunitinib |
|---|---|
| Description | AUC24 is the area under the plasma concentration versus time curve from time zero (predose) to 24 hours postdose (0 to 24). |
| Time Frame | 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD). |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour/milliliter (ng*hr/mL)] |
786.8
(42)
|
| Title | Trough Plasma Concentration (Ctrough) of Sunitinib |
|---|---|
| Description | |
| Time Frame | 0.5 hour predose on Day 1 of Cycle 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD). |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
28.27
(47)
|
| Title | Plasma Concentration at 24 Hours Postdose (C24) of Sunitinib |
|---|---|
| Description | |
| Time Frame | 24 hours postdose on Day 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis Set: Participants who received all scheduled doses of both drugs and completed all required PK assessments in the dose expansion cohort (figitumumab 10 mg/kg + sunitinib 25 mg CDD). |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD (Dose Expansion) |
|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule, until disease progression or unacceptable toxicity. |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
28.87
(53)
|
| Title | Number of Participants With Anti-Drug Antibodies (ADA) |
|---|---|
| Description | Assays for ADA assessment specific for figitumumab would have provided information regarding an immune response to the compound. |
| Time Frame | 0.5 hour pre-infusion on Day 1 in Cycles 1 and 2, at end of treatment, and during the last scheduled follow-up visit (5 months from the last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ADA Analysis Set: Participants who started treatment with study medication and provided at least 1 on-study ADA sample. Due to early termination of the study, ADA samples were not assayed. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants With Objective Response (OR) |
|---|---|
| Description | Objective response (OR) was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR was the complete disappearance of all target and non-target disease, no new lesions, or the normalization of markers (if markers were being followed). PR was greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-target disease, no new lesions, or no reappearance of lesions after a CR. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. |
| Time Frame | Baseline, Day 15 of every 2 cycles until disease progression up to follow-up (approximately 28 days following the last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: All enrolled participants who received at least 1 dose of study medication. |
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 |
|---|---|---|---|---|
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. |
| Measure Participants | 20 | 7 | 12 | 6 |
| Complete Response (CR) |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Partial Response (PR) |
1
2.2%
|
0
NaN
|
1
NaN
|
0
NaN
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. | |||||||
| Arm/Group Title | Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 | ||||
| Arm/Group Description | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule. Dose escalation proceeded to the next cohort if 0/3 or 1/6 participants experienced a DLT. | Figitumumab 10 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 37.5 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg IV on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle on a CDD schedule until disease progression or unacceptable toxicity. | Figitumumab 20 mg/kg on Day 1 of each 3-week cycle plus sunitinib 25 mg oral capsule on Day 1 of each 3-week cycle with 2 weeks of CDD followed by 1 week off, until disease progression or unacceptable toxicity. | ||||
All Cause Mortality |
||||||||
| Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/20 (50%) | 3/7 (42.9%) | 6/12 (50%) | 5/6 (83.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Thrombocytopenia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Cardiac disorders | ||||||||
| Cardio-respiratory arrest | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Pericardial effusion | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Ascites | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Gastrointestinal haemorrhage | 0/20 (0%) | 1/7 (14.3%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Nausea | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Rectal haemorrhage | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Small intestinal perforation | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Vomiting | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| General disorders | ||||||||
| Disease progression | 5/20 (25%) | 0/7 (0%) | 2/12 (16.7%) | 3/6 (50%) | ||||
| Pain | 2/20 (10%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Infections and infestations | ||||||||
| Abdominal wall abscess | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Localised infection | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyperglycaemia | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Fistula | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Nervous system disorders | ||||||||
| Cerebrovascular accident | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal failure | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Ureteric obstruction | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Aspiration | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Epistaxis | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Pulmonary embolism | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Respiratory failure | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/20 (0%) | 1/7 (14.3%) | 1/12 (8.3%) | 1/6 (16.7%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Figitumumab 10 mg/kg + Sunitinib 25 mg CDD | Figitumumab 10 mg/kg + Sunitinib 37.5 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg CDD | Figitumumab 20 mg/kg + Sunitinib 25 mg Schedule 2/1 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 7/7 (100%) | 12/12 (100%) | 6/6 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 7/20 (35%) | 5/7 (71.4%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Iron deficiency anaemia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Leukocytosis | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Leukopenia | 2/20 (10%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Neutropenia | 4/20 (20%) | 2/7 (28.6%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Thrombocytopenia | 7/20 (35%) | 6/7 (85.7%) | 2/12 (16.7%) | 0/6 (0%) | ||||
| Cardiac disorders | ||||||||
| Tachycardia | 0/20 (0%) | 2/7 (28.6%) | 0/12 (0%) | 0/6 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness bilateral | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Tinnitus | 2/20 (10%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypothyroidism | 0/20 (0%) | 1/7 (14.3%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Eye disorders | ||||||||
| Lacrimation increased | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Ocular hyperaemia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Vision blurred | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Visual impairment | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Abdominal pain | 0/20 (0%) | 1/7 (14.3%) | 1/12 (8.3%) | 1/6 (16.7%) | ||||
| Abdominal pain upper | 3/20 (15%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Anorectal discomfort | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Ascites | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Constipation | 2/20 (10%) | 0/7 (0%) | 3/12 (25%) | 0/6 (0%) | ||||
| Diarrhoea | 12/20 (60%) | 5/7 (71.4%) | 7/12 (58.3%) | 2/6 (33.3%) | ||||
| Dry mouth | 3/20 (15%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Duodenogastric reflux | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Dyspepsia | 4/20 (20%) | 2/7 (28.6%) | 2/12 (16.7%) | 0/6 (0%) | ||||
| Dysphagia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Gastritis | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Gastrointestinal haemorrhage | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Gastrooesophageal reflux disease | 4/20 (20%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Gingival bleeding | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Gingival hyperplasia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Gingival inflammation | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Haemorrhoids | 2/20 (10%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hiatus hernia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Ileal perforation | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Intestinal obstruction | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Melaena | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Nausea | 5/20 (25%) | 4/7 (57.1%) | 4/12 (33.3%) | 4/6 (66.7%) | ||||
| Odynophagia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Oral pain | 2/20 (10%) | 0/7 (0%) | 3/12 (25%) | 1/6 (16.7%) | ||||
| Proctalgia | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Rectal haemorrhage | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Salivary hypersecretion | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Stomatitis | 1/20 (5%) | 1/7 (14.3%) | 1/12 (8.3%) | 1/6 (16.7%) | ||||
| Swollen tongue | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Tooth loss | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Vomiting | 4/20 (20%) | 1/7 (14.3%) | 4/12 (33.3%) | 1/6 (16.7%) | ||||
| General disorders | ||||||||
| Asthenia | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Chest pain | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Chills | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Fatigue | 14/20 (70%) | 6/7 (85.7%) | 9/12 (75%) | 5/6 (83.3%) | ||||
| Feeling hot | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Impaired healing | 0/20 (0%) | 1/7 (14.3%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Influenza like illness | 0/20 (0%) | 1/7 (14.3%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Mucosal dryness | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Mucosal inflammation | 4/20 (20%) | 3/7 (42.9%) | 2/12 (16.7%) | 0/6 (0%) | ||||
| Oedema peripheral | 2/20 (10%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Pain | 1/20 (5%) | 1/7 (14.3%) | 2/12 (16.7%) | 0/6 (0%) | ||||
| Performance status decreased | 0/20 (0%) | 3/7 (42.9%) | 0/12 (0%) | 0/6 (0%) | ||||
| Pyrexia | 2/20 (10%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Temperature intolerance | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 2/20 (10%) | 2/7 (28.6%) | 0/12 (0%) | 0/6 (0%) | ||||
| Jaundice | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Infections and infestations | ||||||||
| Ear infection | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Fungal infection | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Genital infection fungal | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Herpes zoster | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Lower respiratory tract infection | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Sinusitis | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Upper respiratory tract infection | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Urinary tract infection | 2/20 (10%) | 1/7 (14.3%) | 3/12 (25%) | 1/6 (16.7%) | ||||
| Viral infection | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Humerus fracture | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Amylase increased | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Aspartate aminotransferase increased | 2/20 (10%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Blood alkaline phosphatase increased | 1/20 (5%) | 2/7 (28.6%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood bilirubin increased | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood calcium decreased | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood creatinine increased | 3/20 (15%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood glucose increased | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood magnesium decreased | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood pressure increased | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Blood testosterone decreased | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Blood uric acid increased | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Electrocardiogram QT prolonged | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Haemoglobin decreased | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Lipase increased | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Platelet count decreased | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Pulmonary arterial pressure increased | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Transaminases increased | 3/20 (15%) | 3/7 (42.9%) | 0/12 (0%) | 0/6 (0%) | ||||
| Weight decreased | 2/20 (10%) | 2/7 (28.6%) | 2/12 (16.7%) | 4/6 (66.7%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 4/20 (20%) | 2/7 (28.6%) | 3/12 (25%) | 2/6 (33.3%) | ||||
| Dehydration | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hyperglycaemia | 3/20 (15%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hyperkalaemia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hyperuricaemia | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypoalbuminaemia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypocalcaemia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypokalaemia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypomagnesaemia | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hyponatraemia | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypophagia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hypophosphataemia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypovolaemia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Iron deficiency | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Malnutrition | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Back pain | 2/20 (10%) | 1/7 (14.3%) | 1/12 (8.3%) | 1/6 (16.7%) | ||||
| Flank pain | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Groin pain | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Muscle spasms | 3/20 (15%) | 1/7 (14.3%) | 5/12 (41.7%) | 0/6 (0%) | ||||
| Musculoskeletal chest pain | 1/20 (5%) | 0/7 (0%) | 2/12 (16.7%) | 0/6 (0%) | ||||
| Musculoskeletal pain | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Musculoskeletal stiffness | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Myalgia | 0/20 (0%) | 0/7 (0%) | 3/12 (25%) | 0/6 (0%) | ||||
| Pain in extremity | 1/20 (5%) | 2/7 (28.6%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Ovarian epithelial cancer | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Nervous system disorders | ||||||||
| Aphasia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Dizziness | 3/20 (15%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Dizziness postural | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Dysgeusia | 12/20 (60%) | 4/7 (57.1%) | 3/12 (25%) | 0/6 (0%) | ||||
| Headache | 0/20 (0%) | 3/7 (42.9%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hyperaesthesia | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Neuropathy peripheral | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Radial nerve palsy | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Restless legs syndrome | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Sinus headache | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Somnolence | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Syncope | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Tremor | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Insomnia | 1/20 (5%) | 2/7 (28.6%) | 0/12 (0%) | 0/6 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Anuria | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Haematuria | 1/20 (5%) | 1/7 (14.3%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hydronephrosis | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Nocturia | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Proteinuria | 4/20 (20%) | 3/7 (42.9%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Renal failure | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Renal failure acute | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Renal impairment | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Urethral obstruction | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Urinary incontinence | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Urinary retention | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Amenorrhoea | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Menorrhagia | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Menstruation delayed | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Pelvic pain | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Vaginal discharge | 2/20 (10%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Vaginal disorder | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Vaginal haemorrhage | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Vulvovaginal discomfort | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Vulvovaginal dryness | 2/20 (10%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Allergic sinusitis | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Cough | 2/20 (10%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Dyspnoea | 4/20 (20%) | 4/7 (57.1%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Dyspnoea exertional | 3/20 (15%) | 2/7 (28.6%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Epistaxis | 3/20 (15%) | 5/7 (71.4%) | 3/12 (25%) | 0/6 (0%) | ||||
| Hiccups | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypoxia | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Laryngospasm | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Nasal congestion | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Oropharyngeal spasm | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Productive cough | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Rhinitis allergic | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Sinus congestion | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Blister | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Dermatitis acneiform | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Dry skin | 0/20 (0%) | 1/7 (14.3%) | 3/12 (25%) | 1/6 (16.7%) | ||||
| Ecchymosis | 1/20 (5%) | 1/7 (14.3%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Erythema | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hair colour changes | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hair growth abnormal | 1/20 (5%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Madarosis | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Night sweats | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 1/20 (5%) | 0/7 (0%) | 3/12 (25%) | 1/6 (16.7%) | ||||
| Petechiae | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Pruritus | 0/20 (0%) | 0/7 (0%) | 0/12 (0%) | 1/6 (16.7%) | ||||
| Rash | 0/20 (0%) | 0/7 (0%) | 2/12 (16.7%) | 0/6 (0%) | ||||
| Rash pruritic | 1/20 (5%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Skin depigmentation | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Skin discolouration | 7/20 (35%) | 3/7 (42.9%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Skin fissures | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Skin lesion | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Skin reaction | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Debridement | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Skin graft | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Vascular disorders | ||||||||
| Haematoma | 0/20 (0%) | 1/7 (14.3%) | 0/12 (0%) | 0/6 (0%) | ||||
| Hypertension | 2/20 (10%) | 3/7 (42.9%) | 2/12 (16.7%) | 1/6 (16.7%) | ||||
| Hypotension | 2/20 (10%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Hypovolaemic shock | 0/20 (0%) | 0/7 (0%) | 1/12 (8.3%) | 0/6 (0%) | ||||
| Orthostatic hypotension | 1/20 (5%) | 0/7 (0%) | 0/12 (0%) | 0/6 (0%) | ||||
Limitations/Caveats
This study was terminated prematurely. Subsequently, ADA samples were not assayed and the pharmacokinetics of sunitinib plus its metabolite were not analyzed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00729833
Other Study ID Numbers:
- A4021024
First Posted:
Aug 8, 2008
Last Update Posted:
Jun 9, 2014
Last Verified:
May 1, 2014