Relative Bioavailability of Pimasertib in Cancer Patients
Sponsor
EMD Serono (Industry)
Overall Status
Completed
CT.gov ID
NCT01992874
Collaborator
(none)
38
1
2
14.9
2.5
Study Details
Study Description
Brief Summary
This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
38 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-Center, Open-Label, Single 60 mg Dose, Two Period, Two Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Two Solid Oral Pimasertib Formulations in Cancer Patients
Actual Study Start Date
:
Nov 30, 2013
Actual Primary Completion Date
:
May 31, 2014
Actual Study Completion Date
:
Feb 28, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pimasertib Capsule/Pimasertib Tablet
|
Drug: Pimasertib Capsule (Part A)
Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.
Other Names:
Drug: Pimasertib Tablet (Part A)
Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.
Other Names:
Drug: Pimasertib Capsule (Part B and trial extension phase)
Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.
Other Names:
|
| Experimental: Pimasertib Tablet/Pimasertib Capsule
|
Drug: Pimasertib Tablet (Part A)
Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.
Other Names:
Drug: Pimasertib Capsule (Part A)
Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A.
Other Names:
Drug: Pimasertib Capsule (Part B and trial extension phase)
Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.
- Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification.
Secondary Outcome Measures
- Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
- Apparent Terminal Half-life (t1/2) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
- Apparent Total Body Clearance (CL/f) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Apparent Volume of Distribution (Vz/f) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
- Terminal Rate Constant (λz) [Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3]
- Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation [From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months]
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.
- Part B: Number of Subjects Who Experienced Complete Response (CR) [Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months]
CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm).
- Part B: Number of Subjects Who Experienced Partial Response (PR) [Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months]
PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters.
- Part B: Number of Subjects Who Experienced Stable Disease (SD) [Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months]
SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference. PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions.
- Part B: Number of Subjects Who Experienced Progressive Disease (PD) [Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months]
PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Pathologically confirmed solid tumors, either refractory to standard therapy or for which no effective standard therapy is available, with a measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
-
An Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (<=) 1
-
Other protocol defined inclusion criteria could apply
Exclusion Criteria:
-
Disease conditions or concomitant medication that may significantly influence the conduct of the trial or an abnormal electrocardiogram (ECG) or blood pressure at Screening as defined in the protocol
-
Treatment with strong inhibitors or inducers of cytochrome P450 2C19 (CYP2C19) and CYP3A4 including fruit juices or beverages containing these substances
-
History of prior mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase (MEK) inhibitor exposure (including, pimasertib) or progression of disease on MEK inhibitors
-
Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of RVO
-
Life expectancy of less than 12 weeks
-
Other protocol defined exclusion criteria could apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Please Contact U.S. Medical Information Located in | Rockland | Massachusetts | United States |
Sponsors and Collaborators
- EMD Serono
Investigators
- Study Director: Medical Responsible, EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
EMD Serono
ClinicalTrials.gov Identifier:
NCT01992874
Other Study ID Numbers:
- 200066-013
First Posted:
Nov 25, 2013
Last Update Posted:
Aug 15, 2017
Last Verified:
Jul 1, 2017
Keywords provided by EMD Serono
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | First/last subject (informed consent): Nov 2013/Feb 2015. Clinical data cut-off: May 2014, Study completion date: Feb 2015 |
|---|---|
| Pre-assignment Detail | A total of 45 subjects were screened. 38 subjects were enrolled and received the trial medication completed two sequence cross-over Part A and further continued in open label Part B. |
| Arm/Group Title | Part A: Pimasertib Capsule Then Pimasertib Tablet | Part A: Pimasertib Tablet Then Pimasertib Capsule | Part B:Pimasertib Capsule |
|---|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally on Day 1 in first intervention period followed by a single dose of 3 Pimasertib 20 mg tablet single dose administered orally on Day 3, of Part A of the study. A washout period of 48 hours was maintained between the administration of the two treatments. | A single dose of 3 Pimasertib 20 mg tablet administered orally on Day 1 in first intervention period followed by a single dose of 2 Pimasertib 30 mg capsule single dose administered orally on Day 3, of Part A of the study. A washout period of 48 hours was maintained between the administration of the two treatments. | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Period Title: Part A | |||
| STARTED | 21 | 17 | 0 |
| COMPLETED | 21 | 17 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
| Period Title: Part A | |||
| STARTED | 0 | 0 | 38 |
| COMPLETED | 0 | 0 | 38 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | It included all the subjects randomized to receive either Pimasertib 60 mg capsule and Pimasertib 60 mg tablet first in Part A and Pimasertib 60 mg capsule in Part B of the study. |
| Overall Participants | 38 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
60.6
(11.74)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
20
52.6%
|
| Male |
18
47.4%
|
Outcome Measures
| Title | Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet. |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 37 | 37 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)] |
254.6
(75.7)
|
314.1
(84.2)
|
| Title | Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf) |
|---|---|
| Description | |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analysed) signifies the number of subjects analysed for this outcome measure. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 32 | 36 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL] |
1110.3
(74.2)
|
1109.2
(72.9)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| Description | |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 37 | 37 |
| Median (Full Range) [hour] |
0.750
|
0.517
|
| Title | Apparent Terminal Half-life (t1/2) |
|---|---|
| Description | |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 32 | 36 |
| Median (Full Range) [hour] |
4.38
|
4.47
|
| Title | Apparent Total Body Clearance (CL/f) |
|---|---|
| Description | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 32 | 36 |
| Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/h)] |
54.041
(74.2)
|
54.092
(72.9)
|
| Title | Apparent Volume of Distribution (Vz/f) |
|---|---|
| Description | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 32 | 36 |
| Geometric Mean (Geometric Coefficient of Variation) [Liter] |
346.454
(54.1)
|
334.540
(59.0)
|
| Title | Terminal Rate Constant (λz) |
|---|---|
| Description | |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 32 | 36 |
| Median (Full Range) [1/h] |
0.16
|
0.15
|
| Title | Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t) |
|---|---|
| Description | Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification. |
| Time Frame | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet |
|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
| Measure Participants | 37 | 37 |
| Geometric Mean (Geometric Coefficient of Variation) [hour*nanogram per milliliter (h*ng/mL)] |
979.0
(76.5)
|
1060.7
(73.0)
|
| Title | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation |
|---|---|
| Description | An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state. |
| Time Frame | From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all subjects who received at least one dose of IMP. |
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet | Part B: Pimasertib Capsule |
|---|---|---|---|
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Measure Participants | 38 | 37 | 38 |
| TEAEs |
19
|
20
|
38
|
| Serious TEAEs |
1
|
0
|
19
|
| TEAEs leading to discontinuation |
0
|
0
|
13
|
| Title | Part B: Number of Subjects Who Experienced Complete Response (CR) |
|---|---|
| Description | CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm). |
| Time Frame | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all subjects who received at least one dose of IMP. |
| Arm/Group Title | Part B: Pimasertib Capsule |
|---|---|
| Arm/Group Description | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Measure Participants | 38 |
| Number [subjects] |
0
|
| Title | Part B: Number of Subjects Who Experienced Partial Response (PR) |
|---|---|
| Description | PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters. |
| Time Frame | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all subjects who received at least one dose of IMP. |
| Arm/Group Title | Part B: Pimasertib Capsule |
|---|---|
| Arm/Group Description | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Measure Participants | 38 |
| Number [subjects] |
1
|
| Title | Part B: Number of Subjects Who Experienced Stable Disease (SD) |
|---|---|
| Description | SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference. PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions. |
| Time Frame | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all subjects who received at least one dose of IMP. |
| Arm/Group Title | Part B: Pimasertib Capsule |
|---|---|
| Arm/Group Description | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Measure Participants | 38 |
| Number [subjects] |
10
|
| Title | Part B: Number of Subjects Who Experienced Progressive Disease (PD) |
|---|---|
| Description | PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions. |
| Time Frame | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all subjects who received at least one dose of IMP. |
| Arm/Group Title | Part B: Pimasertib Capsule |
|---|---|
| Arm/Group Description | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Measure Participants | 38 |
| Number [subjects] |
15
|
Adverse Events
| Time Frame | Baseline up to end of trial (before the start of a new anticancer therapy or 30 ± 2 days after the last investigational medicinal product administration.) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet | Part B: Pimasertib Capsule (BID) | |||
| Arm/Group Description | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. | |||
All Cause Mortality |
||||||
| Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet | Part B: Pimasertib Capsule (BID) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet | Part B: Pimasertib Capsule (BID) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/38 (2.6%) | 0/37 (0%) | 19/38 (50%) | |||
| Cardiac disorders | ||||||
| Cardiac failure congestive | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 1/38 (2.6%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Abdominal pain upper | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Gastrointestinal haemorrhage | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Rectal haemorrhage | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Small intestinal obstruction | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Non-cardiac chest pain | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| General disorders | ||||||
| Pyrexia | 1/38 (2.6%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Disease progression | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Fatigue | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Oedema peripheral | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Infections and infestations | ||||||
| Pneumonia klebsiella | 1/38 (2.6%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Septic shock | 1/38 (2.6%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Bronchitis | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Pyelonephritis | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase increased | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Malignant ascites | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Tumour pain | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Nervous system disorders | ||||||
| Seizure | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Syncope | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Hypoxia | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Pleural effusion | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Pneumonitis | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Pneumothorax | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Pulmonary embolism | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Pulmonary hypertension | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Hypotension | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Deep vein thrombosis | 0/38 (0%) | 0/37 (0%) | 1/38 (2.6%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Part A: Pimasertib 60 mg Capsule | Part A: Pimasertib 60 mg Tablet | Part B: Pimasertib Capsule (BID) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/38 (47.4%) | 17/37 (45.9%) | 37/38 (97.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Iron deficiency anaemia | 1/38 (2.6%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Anaemia | 1/38 (2.6%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Thrombocytopenia | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Eye disorders | ||||||
| Vision blurred | 1/38 (2.6%) | 4/37 (10.8%) | 7/38 (18.4%) | |||
| Retinal detachment | 0/38 (0%) | 0/37 (0%) | 9/38 (23.7%) | |||
| Visual impairment | 2/38 (5.3%) | 1/37 (2.7%) | 3/38 (7.9%) | |||
| Chorioretinopathy | 0/38 (0%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Macular detachment | 0/38 (0%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Dry eye | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Colour blindness acquired | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Periorbital oedema | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Retinal exudates | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 2/38 (5.3%) | 6/37 (16.2%) | 22/38 (57.9%) | |||
| Nausea | 3/38 (7.9%) | 2/37 (5.4%) | 13/38 (34.2%) | |||
| Vomiting | 1/38 (2.6%) | 0/37 (0%) | 9/38 (23.7%) | |||
| Stomatitis | 1/38 (2.6%) | 0/37 (0%) | 7/38 (18.4%) | |||
| Constipation | 0/38 (0%) | 1/37 (2.7%) | 2/38 (5.3%) | |||
| Dry mouth | 1/38 (2.6%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Abdominal pain | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Ascites | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| General disorders | ||||||
| Fatigue | 2/38 (5.3%) | 0/37 (0%) | 20/38 (52.6%) | |||
| Oedema peripheral | 0/38 (0%) | 0/37 (0%) | 10/38 (26.3%) | |||
| Pyrexia | 1/38 (2.6%) | 0/37 (0%) | 8/38 (21.1%) | |||
| Chills | 1/38 (2.6%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Non-cardiac chest pain | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Early satiety | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Oral candidiasis | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Rash pustular | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Upper respiratory tract infection | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase increased | 0/38 (0%) | 0/37 (0%) | 17/38 (44.7%) | |||
| Blood creatinine increased | 1/38 (2.6%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Gamma-glutamyltransferase increased | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Transaminases increased | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/38 (2.6%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Hypomagnesaemia | 0/38 (0%) | 1/37 (2.7%) | 2/38 (5.3%) | |||
| Dehydration | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Hypokalaemia | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Hyponatraemia | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Hypovolaemia | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscular weakness | 0/38 (0%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Arthralgia | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Back pain | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Nervous system disorders | ||||||
| Dizziness | 0/38 (0%) | 1/37 (2.7%) | 7/38 (18.4%) | |||
| Headache | 1/38 (2.6%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Neuropathy peripheral | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Syncope | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Psychiatric disorders | ||||||
| Mental status changes | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Confusional state | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea exertional | 0/38 (0%) | 1/37 (2.7%) | 6/38 (15.8%) | |||
| Cough | 0/38 (0%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Pleural effusion | 0/38 (0%) | 0/37 (0%) | 4/38 (10.5%) | |||
| Dyspnoea | 1/38 (2.6%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Oropharyngeal pain | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 1/38 (2.6%) | 1/37 (2.7%) | 13/38 (34.2%) | |||
| Dermatitis acneiform | 0/38 (0%) | 0/37 (0%) | 6/38 (15.8%) | |||
| Rash maculo-papular | 0/38 (0%) | 0/37 (0%) | 5/38 (13.2%) | |||
| Pruritus | 0/38 (0%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Palmar-plantar erythrodysaesthesia syndrome | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Rash erythematous | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Swelling face | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
| Vascular disorders | ||||||
| Hypotension | 2/38 (5.3%) | 0/37 (0%) | 3/38 (7.9%) | |||
| Hypertension | 0/38 (0%) | 0/37 (0%) | 2/38 (5.3%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Merck KGaA Communication Center |
|---|---|
| Organization | Merck KGaA |
| Phone | +49-6151-72-5200 |
| service@merckgroup.com |
Responsible Party:
EMD Serono
ClinicalTrials.gov Identifier:
NCT01992874
Other Study ID Numbers:
- 200066-013
First Posted:
Nov 25, 2013
Last Update Posted:
Aug 15, 2017
Last Verified:
Jul 1, 2017