Trial Outcomes & Findings for MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1 (NCT NCT02096471)
NCT ID: NCT02096471
Last Updated: 2019-01-10
Results Overview
Response is assessed by the NCI-POB at the time that follow-up 3D-MRI scans are performed (after course 4, 8, 12, and then after completion of every 6 courses thereafter). For the purpose of determining the level of response (complete, partial, etc.) measurements from the follow-up scans are compared to the target lesion size in the pretreatment MRI scan using 3D data analysis.Complete Response (CR): A complete resolution of the target plexiform neurofibroma for ≥ 4 weeks Partial Response (PR): A ≥20% reduction in the volume of the target plexiform neurofibroma lesion for ≥4 weeks. Stable Disease (SD): A \<20% increase, and \< 20% decrease in the volume of the target plexiform neurofibroma lesion for ≥4 weeks. Progressive Disease (PD): A ≥ 20% increase in the volume (by 3D-MRI) of the target plexiform neurofibroma compared to the pretreatment volume..
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
baseline to 24 months
Results posted on
2019-01-10
Participant Flow
The study required at least 1 partial or complete response within the first 9 patients in order to complete recruitment.
Unit of analysis: Target Lesion
Participant milestones
| Measure |
Agent PD-0325901
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Overall Study
STARTED
|
19 19
|
|
Overall Study
COMPLETED
|
6 6
|
|
Overall Study
NOT COMPLETED
|
13 13
|
Reasons for withdrawal
| Measure |
Agent PD-0325901
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lack of Efficacy
|
7
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Non-Compliant
|
2
|
Baseline Characteristics
MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1
Baseline characteristics by cohort
| Measure |
Agent PD-0325901
n=19 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
24.9 years
STANDARD_DEVIATION 6.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 Participants
n=5 Participants
|
|
MRI at Baseline
1 Target Number of Plexiform Neurofibromas
|
17 Participants
n=5 Participants
|
|
MRI at Baseline
1 Target and non target Plexiform Neurofibromas
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to 24 monthsPopulation: All 19 participants enrolled equivalent to intention to treat population
Response is assessed by the NCI-POB at the time that follow-up 3D-MRI scans are performed (after course 4, 8, 12, and then after completion of every 6 courses thereafter). For the purpose of determining the level of response (complete, partial, etc.) measurements from the follow-up scans are compared to the target lesion size in the pretreatment MRI scan using 3D data analysis.Complete Response (CR): A complete resolution of the target plexiform neurofibroma for ≥ 4 weeks Partial Response (PR): A ≥20% reduction in the volume of the target plexiform neurofibroma lesion for ≥4 weeks. Stable Disease (SD): A \<20% increase, and \< 20% decrease in the volume of the target plexiform neurofibroma lesion for ≥4 weeks. Progressive Disease (PD): A ≥ 20% increase in the volume (by 3D-MRI) of the target plexiform neurofibroma compared to the pretreatment volume..
Outcome measures
| Measure |
Agent PD-0325901
n=19 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Percent of Participants With a 20% or More Change in Target Tumor Volume
Complete response
|
0 Participants
|
|
Percent of Participants With a 20% or More Change in Target Tumor Volume
Partial response
|
8 Participants
|
|
Percent of Participants With a 20% or More Change in Target Tumor Volume
Stable response
|
11 Participants
|
|
Percent of Participants With a 20% or More Change in Target Tumor Volume
Progressive Disease
|
0 Participants
|
SECONDARY outcome
Timeframe: baseline to 24 monthsPopulation: ITT
Number of Evaluable Patients at 24 Months: Any subject with ≥ one dose of PD-0325901 and had a ≥ Grade 3 associated toxicity is evaluable for toxicity. In the absence of a ≥ Grade 3 toxicity, any subject who completed one full course of therapy is evaluable for toxicity. Evaluable For Response - Subjects who have completed at least two courses of therapy and have had their first follow-up MRI evaluation. Subjects who did not respond and are later found to have a target tumor other than a plexiform neurofibroma (e.g. malignant peripheral nerve sheath tumor) are not evaluable for response. Evaluable for Pharmacokinetics - Any subject who has at least 4 samples drawn for pharmacokinetics is evaluable for pharmacokinetics. Evaluable for Pharmacodynamics - Any subject who has a dermal neurofibroma biopsy for pharmacodynamics prior to starting therapy plus at least one other dermal neurofibroma biopsy is evaluable for
Outcome measures
| Measure |
Agent PD-0325901
n=19 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Evaluable Participants Treated With PD-0325901
Evaluable
|
8 Participants
|
|
Evaluable Participants Treated With PD-0325901
Failed to Achieve Comp/Partial Response
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline to 24 MonthsNumber and Percent of Participants with AEs and SAEs
Outcome measures
| Measure |
Agent PD-0325901
n=19 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Toxicity of PD-0325901
SAEs
|
2 participants
|
|
Toxicity of PD-0325901
AEs
|
19 participants
|
SECONDARY outcome
Timeframe: Baseline to 24 MonthsPopulation: All participants were evaluated and the two with non-Plexiform Neurofibromas were assessed.
radiographic response based on volumetric MRI measurements of up to 2 Non Target Plexiform Neurofibromas classified as complete, partial, stable or progressive
Outcome measures
| Measure |
Agent PD-0325901
n=19 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
The Objective Response Rate of up to 2 Non-Target Plexiform Neurofibromas to PD-0325901
Complete response
|
0 participants
|
|
The Objective Response Rate of up to 2 Non-Target Plexiform Neurofibromas to PD-0325901
Partial response
|
0 participants
|
|
The Objective Response Rate of up to 2 Non-Target Plexiform Neurofibromas to PD-0325901
Stable response
|
2 participants
|
|
The Objective Response Rate of up to 2 Non-Target Plexiform Neurofibromas to PD-0325901
Progressive Disease
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1; Course 1Population: 18 of the 19 participants had PK samples drawn.
Mean and Standard Deviation AUC Estimates of the levels of PD-0325901 over 12-Hours for both the Parent and Metabolite Compound, based on samples at Pre-dose, .5 Hr. Post dose, 1.0 Hr.Post dose, 2.0 Hr.Post dose, 3.0 Hr. Post dose, 4.0 Hr.Post dose, 6.0 Hr. Post dose, 8.0 Hr. Post dose, 10.0-12.0 Hr. Post dose.
Outcome measures
| Measure |
Agent PD-0325901
n=18 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Area Under the Curve for the Parent Compound
|
219.1 ng/mL*hr/(mg/m^2Parent)
Standard Deviation 41.4
|
SECONDARY outcome
Timeframe: Baseline to 12 MonthsPopulation: NRS-11 are on a scale of 0-10 with 0 being no pain, higher scores are greater intensity. BPI pain interference scale yields a total score (each item 0-10 and total score=mean all items) higher scores are more pain interference.Remaining items are initially a 5-point Likert scale (0-4) and transformed to a 0-100 scale with higher scores better QOL.
The PedsQL™ NF1 Module asks how much of a problem each item has been during the past one month. A 5-point response scale: 0= never a problem...4= almost always a problem). Items are reverse scored and linearly transformed to a scale of 0-100 Higher scores = better HRQOL. The total scale score is the sum of items divided by the number answered. Subscale scores are computed similarly. If more than 50% of the items in the scale are missing, the scale score is not computed. The Numerical Rating Scale-11 (NRS-11) is a self-report segmented 11-point numeric scale that assesses pain intensity with 0 representing "no pain" at the right end of the line and 10 representing "worst pain you can imagine". The Brief Pain Inventory (BPI)-Pain Interference Scale is a 7-item self-report questionnaire asking (general activity, mood, walking, normal work, relations with other people, sleep, and enjoyment of life) in the past week with 0 = no interference and 10 = completely interferes.
Outcome measures
| Measure |
Agent PD-0325901
n=19 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Daily Activities (Baseline - 12 mo.)
|
6.66 score on a scale
Standard Error 5.05
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Emotional Functioning (Baseline - 12 mo.)
|
-2.34 score on a scale
Standard Error 6.46
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Social Functioning (Baseline - 12 mo.)
|
-6.24 score on a scale
Standard Error 6.79
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Cognitive Functioning (Baseline - 12 mo.)
|
-0.17 score on a scale
Standard Error 6.37
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Communication Functioning (Baseline - 12 mo.)
|
0.68 score on a scale
Standard Error 7.99
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Worry (Baseline - 12 mo.)
|
-10.97 score on a scale
Standard Error 8.16
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Paresthesias (Baseline - 12 mo.)
|
-3.74 score on a scale
Standard Error 6.58
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Skin Irritation (Baseline - 12 mo.)
|
-4.21 score on a scale
Standard Error 5.51
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Sensation (Baseline - 12 mo.)
|
-6.27 score on a scale
Standard Error 5.72
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Fatigue (Baseline - 12 mo.)
|
-0.71 score on a scale
Standard Error 8.52
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Treatment Anxiety (Baseline - 12 mo.)
|
-1.07 score on a scale
Standard Error 7.53
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Overall Tumor Pain Change (Baseline - 12 mo.)
|
1.38 score on a scale
Standard Error 0.84
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Most Important Tumor Pain (Baseline - 12 mo.)
|
2.10 score on a scale
Standard Error 0.80
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Brief Pain Inventory (Baseline - 12 mo.)
|
0.89 score on a scale
Standard Error 0.66
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Total Functioning (Baseline - 12 mo.)
|
-3.77 score on a scale
Standard Error 3.60
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Physical Functioning (Baseline - 12 mo.)
|
-3.55 score on a scale
Standard Error 6.87
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Pain and Hurt (Baseline - 12 mo.)
|
-13.06 score on a scale
Standard Error 8.29
|
|
Quality of Life Using the Pain Subscale of the NRS-11 and PedsQL™ NF1 for Subjects Receiving PD-0325901 Using Age-based Assessments
Movement and Balance (Baseline - 12 mo.)
|
-12.98 score on a scale
Standard Error 6.35
|
SECONDARY outcome
Timeframe: Day 1; Course 1Population: 18 of the 19 participants had PK samples collected and the metabolite compound AUC was computed and summarized.
Mean 12-Hour AUC Estimates of the Parent and Metabolite Compound, based on samples at Pre-dose, .5 Hr. Post dose, 1.0 Hr.Post dose, 2.0 Hr.Post dose, 3.0 Hr. Post dose, 4.0 Hr.Post dose, 6.0 Hr. Post dose, 8.0 Hr. Post dose, 10.0-12.0 Hr. Post dose.
Outcome measures
| Measure |
Agent PD-0325901
n=18 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Area Under the Curve for the Metabolite Compound
|
91.1 ng/mL*hr/(mg/m^2 Metabolite)
Standard Deviation 49.5
|
SECONDARY outcome
Timeframe: Day 1; Course 1Population: 18 of the 19 participants had PK samples collected and the metabolite compound AUC was computed and summarized.
Half life Estimates of PD-0325901 of the Parent and Metabolite Compound, based on samples at Pre-dose, .5 Hr. Post dose, 1.0 Hr.Post dose, 2.0 Hr.Post dose, 3.0 Hr. Post dose, 4.0 Hr.Post dose, 6.0 Hr. Post dose, 8.0 Hr. Post dose, 10.0-12.0 Hr. Post dose.
Outcome measures
| Measure |
Agent PD-0325901
n=18 Participants
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Mean Half-Life for the PD-0325901 Concentrations
|
6.1 hours
Standard Deviation 3.5
|
Adverse Events
Agent PD-0325901
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Agent PD-0325901
n=19 participants at risk
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
5.3%
1/19 • Number of events 1 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
5.3%
1/19 • Number of events 1 • Baseline to 24 Months
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions, other
|
5.3%
1/19 • Number of events 1 • Baseline to 24 Months
|
Other adverse events
| Measure |
Agent PD-0325901
n=19 participants at risk
The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study.
PD-0325901
|
|---|---|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
26.3%
5/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
21.1%
4/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hyerkalemia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
21.1%
4/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
21.1%
4/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
10.5%
2/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
10.5%
2/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
15.8%
3/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Fibrosis Deep Connective Tissue
|
5.3%
1/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
5.3%
1/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders - Other, Hip Pain
|
5.3%
1/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
21.1%
4/19 • Baseline to 24 Months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (inc cysts and polyps) - Other, Cyst
|
5.3%
1/19 • Baseline to 24 Months
|
|
Blood and lymphatic system disorders
Anemia
|
15.8%
3/19 • Baseline to 24 Months
|
|
Blood and lymphatic system disorders
Hemolysis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Cardiac disorders
Sinus Tachycardia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Ear and labyrinth disorders
Ear Pain
|
10.5%
2/19 • Baseline to 24 Months
|
|
Ear and labyrinth disorders
Vertigo
|
5.3%
1/19 • Baseline to 24 Months
|
|
Eye disorders
Eye Disorder - Other, Pigment Changes
|
5.3%
1/19 • Baseline to 24 Months
|
|
Eye disorders
Eye Disorder - Other, Subconjunctival Hemmorrhage of the Eye
|
5.3%
1/19 • Baseline to 24 Months
|
|
Eye disorders
Eye Disorders - Other, Choroidal Space Macular
|
5.3%
1/19 • Baseline to 24 Months
|
|
Eye disorders
Eye Disorders - Other, Nuclear Lens Opacification
|
5.3%
1/19 • Baseline to 24 Months
|
|
Eye disorders
Eye Disorders - Other, Optic Nerve Drusen
|
5.3%
1/19 • Baseline to 24 Months
|
|
Eye disorders
Eye Pain
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Abdominal Distension
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Abdominal Pain
|
15.8%
3/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Bloating
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Constipation
|
21.1%
4/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Diarrhea
|
31.6%
6/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Dry Mouth
|
10.5%
2/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Dyspepsia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Gastritis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Blood in Stool
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Duodenitis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Gastroparesis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Mucositis oral
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Nausea
|
63.2%
12/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Oral Pain
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Rectal hemmorrhage
|
5.3%
1/19 • Baseline to 24 Months
|
|
Gastrointestinal disorders
Vomitting
|
36.8%
7/19 • Baseline to 24 Months
|
|
General disorders
Chills
|
5.3%
1/19 • Baseline to 24 Months
|
|
General disorders
Edema Face
|
5.3%
1/19 • Baseline to 24 Months
|
|
General disorders
Edema Limbs
|
10.5%
2/19 • Baseline to 24 Months
|
|
General disorders
Fatigue
|
57.9%
11/19 • Baseline to 24 Months
|
|
General disorders
Flu-like Symptoms
|
15.8%
3/19 • Baseline to 24 Months
|
|
General disorders
Localized Edema
|
5.3%
1/19 • Baseline to 24 Months
|
|
General disorders
Pain
|
10.5%
2/19 • Baseline to 24 Months
|
|
Infections and infestations
Conjunctivitis Infective
|
5.3%
1/19 • Baseline to 24 Months
|
|
Infections and infestations
Mucosal Infection
|
5.3%
1/19 • Baseline to 24 Months
|
|
Infections and infestations
Paronychia
|
10.5%
2/19 • Baseline to 24 Months
|
|
Infections and infestations
Sinusitis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Infections and infestations
Tooth Infection
|
5.3%
1/19 • Baseline to 24 Months
|
|
Infections and infestations
Upper Respiratory Infection
|
15.8%
3/19 • Baseline to 24 Months
|
|
Investigations
Alkaline Phosphatase Increased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Aspartate Aminotransferase Increased
|
10.5%
2/19 • Baseline to 24 Months
|
|
Nervous system disorders
Dizziness
|
31.6%
6/19 • Baseline to 24 Months
|
|
Nervous system disorders
Headache
|
42.1%
8/19 • Baseline to 24 Months
|
|
Nervous system disorders
Movements involuntary
|
5.3%
1/19 • Baseline to 24 Months
|
|
Nervous system disorders
Paresthesia
|
10.5%
2/19 • Baseline to 24 Months
|
|
Nervous system disorders
Seizure
|
10.5%
2/19 • Baseline to 24 Months
|
|
Nervous system disorders
Spasticity
|
5.3%
1/19 • Baseline to 24 Months
|
|
Nervous system disorders
Syncope
|
5.3%
1/19 • Baseline to 24 Months
|
|
Psychiatric disorders
Agitation
|
5.3%
1/19 • Baseline to 24 Months
|
|
Psychiatric disorders
Anxiety
|
5.3%
1/19 • Baseline to 24 Months
|
|
Psychiatric disorders
Confusion
|
5.3%
1/19 • Baseline to 24 Months
|
|
Psychiatric disorders
Insomnia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Renal and urinary disorders
Cystitis noninfective
|
5.3%
1/19 • Baseline to 24 Months
|
|
Renal and urinary disorders
Urinary incontinence
|
5.3%
1/19 • Baseline to 24 Months
|
|
Reproductive system and breast disorders
Irregular menstruation
|
5.3%
1/19 • Baseline to 24 Months
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - other, breakthrough bleeding
|
5.3%
1/19 • Baseline to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.5%
2/19 • Baseline to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.5%
2/19 • Baseline to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
10.5%
2/19 • Baseline to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Alpecia
|
10.5%
2/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Hirsutism
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.8%
3/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Rash maculopapular
|
10.5%
2/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
94.7%
18/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Rash pustular
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Bleeding and oozing from ear
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Erythema hallux
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Erythema
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Hemangiomas
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Oily Skin
|
5.3%
1/19 • Baseline to 24 Months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Pustular Dermatosis
|
5.3%
1/19 • Baseline to 24 Months
|
|
Vascular disorders
Hypertension
|
10.5%
2/19 • Baseline to 24 Months
|
|
Vascular disorders
Vascular disorder - Other, Hot Flashes
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Blood Bilirubin Increased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
CPK Increased
|
31.6%
6/19 • Baseline to 24 Months
|
|
Investigations
Creatinine Increased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Hemoglobin Increased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Hiatal Hernia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Indigestion
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Investigations - Other, Total Protein Serum High
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Lymphocyte Count Decreased
|
10.5%
2/19 • Baseline to 24 Months
|
|
Investigations
Lymphocyte Count Increased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Neutrophil Count Decreased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Investigations
Platelet Count Decreased
|
10.5%
2/19 • Baseline to 24 Months
|
|
Investigations
Weight Gain
|
15.8%
3/19 • Baseline to 24 Months
|
|
Investigations
White Blood Cell Count Decreased
|
5.3%
1/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Anorexia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Dehydration
|
5.3%
1/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
5.3%
1/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
21.1%
4/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
10.5%
2/19 • Baseline to 24 Months
|
|
Metabolism and nutrition disorders
Hypernatermia
|
5.3%
1/19 • Baseline to 24 Months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60