Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
pancreatic cancer
Brief summary
The purpose of this study is to evaluate the safety and efficacy of abemaciclib alone and in combination with other drugs versus standard of care in participants with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
Interventions
DRUGAbemaciclib
Administered orally
DRUGLY3023414
Administered orally
DRUGGemcitabine
Administered IV
DRUGCapecitabine
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological diagnosis of ductal adenocarcinoma of the pancreas. * Metastatic disease with documented disease progression following previous treatment with at least one, but no more than 2 prior therapies, with one of the prior therapies having been either gemcitabine-based or fluoropyrimidine-based therapy. Neoadjuvant and/or adjuvant therapies for localized resectable or unresectable PDAC each count as a line of therapy if multiagent chemotherapy regimens were administered (and neoadjuvant regimen was different than adjuvant regimen) and if the participant progressed with metastatic disease while taking or within 6 months of completion of (neo)adjuvant therapy. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Participant for whom treatment with monotherapy chemotherapy such as gemcitabine or capecitabine is a reasonable choice. * Discontinued all prior treatment for cancer at least 14 days prior to initial dose of study treatment. * Adequate organ function. * allow alanine aminotransferase (ALT) or aspartate aminotransferase (AST) up to 5x upper limit of normal (ULN) if liver metastases. * allow bilirubin up to 2.5 times ULN if elevation is not associated with other signs of liver toxicity or can be explained by mechanical obstruction - requires clinical research physician approval.
Exclusion criteria
* Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for \>30 days prior to study treatment initiation are eligible. * Have insulin-dependent diabetes mellitus. Participants with type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c (HbA1c) \<7%. * Have symptomatic central nervous system metastasis. Screening of asymptomatic participants is not required for enrollment. * Have had major surgery within 7 days prior to initiation of study drug to allow for postoperative healing of the surgical wound and site(s). * Have previously received treatment with any cyclin-dependent kinase (CDK) 4 and 6 inhibitor or phosphatidylinositol 3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor or have a known hypersensitivity to any component of the investigational products in this study. * Have a known hypersensitivity to investigator's choice of standard of care (gemcitabine or capecitabine).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months) | Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. |
| Stage 2: Progression Free Survival (PFS) | Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months) | PFS was defined as the time from the date of randomization until first observation of objective progressive disease as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a patient does not have a complete baseline disease assessment, then the PFS time will be censored at the randomization date, regardless of whether or not objectively determined disease progression or death has been observed for the patient; otherwise, if a patient is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time will be censored at the last complete objective progression-free disease assessment date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414 | Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles) | — |
| Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414 | Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles) | — |
| Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD | Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months) | — |
| Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months | Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months) | Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD ≥6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
| Stage 2: Duration of Response (DoR) | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months) | — |
| Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months) | Objective response rate (ORR) is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. |
| Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level | Baseline, 6 Months | No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
| Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Baseline, 6 Months | mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours, and typical completion time for this instrument is less than 5 minutes. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
| Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Baseline, 6 Months | The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: 1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). 2. Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much) 3. Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
| Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 | C2D1: 0h, C3D1: 0h, C4D1: 0h | Mean steady state exposure was reported by trough pre-dose plasma concentrations. |
| Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose | C1D1: 2h Post dose | Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose. |
| Stage 2: Overall Survival (OS) | Baseline to Death from Any Cause (Up to 10 Months) | OS duration is measured from the date of randomization to the date of death from any cause. for participants who is not known to have died as of the data-inclusion cutoff date, OS was censored at the last known alive date. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. |
| Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) | Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose | Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax). |
Countries
Australia, Belgium, France, Israel, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Study was planned for stage 1 & stage 2. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. Completed participants are those who has CR, PR, SD, or PD and is off treatment.
Pre-assignment details
Per protocol, no efficacy analysis was planned for safety lead in. Purpose of safety lead in was only safety evaluation. All efficacy was done on randomized pts.
Participants by arm
| Arm | Count |
|---|---|
| 150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in) Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle. | 7 |
| 200mg Abemaciclib Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles. | 33 |
| 150mg Abemaciclib + 150mg LY3023414 Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles. | 33 |
| Gemcitabine or Capecitabine Participants received either 1000 milligram per square meter (mg/m\^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m\^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle. | 33 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 9 | 9 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Randomized, Never Treated | 0 | 1 | 0 | 7 |
| Overall Study | Study closed by sponsor | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | 200mg Abemaciclib | 150mg Abemaciclib + 150mg LY3023414 | 150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in) | Gemcitabine or Capecitabine | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.09 years STANDARD_DEVIATION 7.83 | 62.52 years STANDARD_DEVIATION 8.97 | 65.29 years STANDARD_DEVIATION 6.99 | 66.85 years STANDARD_DEVIATION 7.61 | 63.40 years STANDARD_DEVIATION 8.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 0 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 28 Participants | 7 Participants | 24 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 5 Participants | 0 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 26 Participants | 26 Participants | 7 Participants | 25 Participants | 84 Participants |
| Region of Enrollment Australia | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Belgium | 8 Participants | 6 Participants | 0 Participants | 5 Participants | 19 Participants |
| Region of Enrollment France | 1 Participants | 1 Participants | 0 Participants | 6 Participants | 8 Participants |
| Region of Enrollment Israel | 2 Participants | 4 Participants | 0 Participants | 5 Participants | 11 Participants |
| Region of Enrollment Spain | 5 Participants | 7 Participants | 0 Participants | 3 Participants | 15 Participants |
| Region of Enrollment Taiwan | 7 Participants | 4 Participants | 0 Participants | 3 Participants | 14 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 8 Participants | 10 Participants | 7 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 4 Participants | 19 Participants | 57 Participants |
| Sex: Female, Male Male | 15 Participants | 17 Participants | 3 Participants | 14 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 7 | 22 / 32 | 21 / 33 | 12 / 26 |
| other Total, other adverse events | 7 / 7 | 30 / 32 | 33 / 33 | 25 / 26 |
| serious Total, serious adverse events | 4 / 7 | 17 / 32 | 18 / 33 | 15 / 26 |
Outcome results
Primary
Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200mg Abemaciclib | Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | 15.2 percentage of Participants |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | 12.1 percentage of Participants |
| Gemcitabine or Capecitabine | Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | 36.4 percentage of Participants |
p-value: 0.0495Cochran-Mantel-Haenszel
p-value: 0.023Cochran-Mantel-Haenszel
Primary
Stage 2: Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization until first observation of objective progressive disease as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a patient does not have a complete baseline disease assessment, then the PFS time will be censored at the randomization date, regardless of whether or not objectively determined disease progression or death has been observed for the patient; otherwise, if a patient is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time will be censored at the last complete objective progression-free disease assessment date.
Time frame: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)
Population: All randomized participants. Censored participants: Abemaciclib 200 mg: 3, Abemaciclib 150mg + LY3023414 150mg: 8, Gemcitabine \& Capecitabine: 18; No participants were enrolled in stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled in stage 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200mg Abemaciclib | Stage 2: Progression Free Survival (PFS) | 1.68 Months |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Progression Free Survival (PFS) | 1.81 Months |
| Gemcitabine or Capecitabine | Stage 2: Progression Free Survival (PFS) | 3.25 Months |
p-value: 0.0085Log Rank
p-value: 0.0123Log Rank
Secondary
Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR
Objective response rate (ORR) is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
Time frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200mg Abemaciclib | Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR | 3 percentage of Participants |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR | 0 percentage of Participants |
| Gemcitabine or Capecitabine | Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR | 3 percentage of Participants |
p-value: 1Cochran-Mantel-Haenszel
p-value: 0.3017Cochran-Mantel-Haenszel
Secondary
Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20))
Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax).
Time frame: Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose
Population: All randomized participants who received at least one dose of Abemaciclib along with Galunisertib and had evaluable PK samples.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200mg Abemaciclib | Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) | Abemaciclib | 356 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 137 |
| 200mg Abemaciclib | Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) | LSN2839567 (M2) | 85.1 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 66 |
| 200mg Abemaciclib | Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) | LSN3106726 (M20) | 153 Nanogram per Millilitre (ng/mL) | Geometric Coefficient of Variation 58 |
Secondary
Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414
Time frame: Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)
Population: Zero Participants Analyzed: AUC cannot be calculated due to insufficient data collected.
Secondary
Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414
Time frame: Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)
Population: Zero Participants Analyzed: Cmax cannot be calculated due to insufficient data collected.
Secondary
Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose
Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose.
Time frame: C1D1: 2h Post dose
Population: All randomized participants who received at least one dose of 150mg LY3023414 and had evaluable PK samples.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200mg Abemaciclib | Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose | 518 ng/mL | Geometric Coefficient of Variation 67 |
Secondary
Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414
Mean steady state exposure was reported by trough pre-dose plasma concentrations.
Time frame: C2D1: 0h, C3D1: 0h, C4D1: 0h
Population: All randomized participants who received at least one dose of 150mg LY3023414 and had evaluable PK samples.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200mg Abemaciclib | Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 | 27.3 ng/mL | Geometric Coefficient of Variation 450 |
Secondary
Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level
No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time frame: Baseline, 6 Months
Population: All randomized participants with baseline and post baseline CA 19-9 measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 200mg Abemaciclib | Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level | 4281.53 U/mL | Standard Deviation 8177.89 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level | 3225.29 U/mL | Standard Deviation 5730.25 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level | -501.17 U/mL | Standard Deviation 7198.7 |
Secondary
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)
mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours, and typical completion time for this instrument is less than 5 minutes. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time frame: Baseline, 6 Months
Population: All randomized participants with baseline \& post baseline value for the mBPI-sf specified item.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | BPI Mean Pain Interference Score | 0.55 score on a scale | Standard Error 0.44 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain at its Worst in Last 24 hours | 0.63 score on a scale | Standard Error 0.47 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain at its Least in Last 24 hours | 0.86 score on a scale | Standard Error 0.42 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain on the Average | 0.62 score on a scale | Standard Error 0.45 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Right Now | 0.38 score on a scale | Standard Error 0.34 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered General Activity | 0.64 score on a scale | Standard Error 0.47 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Mood | 0.54 score on a scale | Standard Error 0.41 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered Walking Ability | 0.05 score on a scale | Standard Error 0.55 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Normal Work | 1.07 score on a scale | Standard Error 0.51 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Relations | 0.39 score on a scale | Standard Error 0.52 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Sleep | 0.19 score on a scale | Standard Error 0.53 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered Enjoyment of Life | 0.69 score on a scale | Standard Error 0.62 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered Enjoyment of Life | 0.39 score on a scale | Standard Error 0.72 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | BPI Mean Pain Interference Score | 0.50 score on a scale | Standard Error 0.51 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Mood | 0.28 score on a scale | Standard Error 0.48 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Normal Work | 0.66 score on a scale | Standard Error 0.59 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain at its Worst in Last 24 hours | -0.33 score on a scale | Standard Error 0.55 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered General Activity | 0.07 score on a scale | Standard Error 0.55 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Sleep | 0.34 score on a scale | Standard Error 0.61 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain at its Least in Last 24 hours | 0.18 score on a scale | Standard Error 0.49 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered Walking Ability | 0.83 score on a scale | Standard Error 0.64 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Right Now | 0.34 score on a scale | Standard Error 0.59 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain on the Average | -0.03 score on a scale | Standard Error 0.51 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Relations | 0.67 score on a scale | Standard Error 0.61 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain on the Average | -0.07 score on a scale | Standard Error 0.53 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Right Now | -0.38 score on a scale | Standard Error 0.61 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Relations | 0.26 score on a scale | Standard Error 0.63 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered General Activity | 0.22 score on a scale | Standard Error 0.57 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Mood | 0.60 score on a scale | Standard Error 0.5 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered Walking Ability | 0.19 score on a scale | Standard Error 0.67 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Sleep | -0.56 score on a scale | Standard Error 0.65 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | BPI Mean Pain Interference Score | 0.05 score on a scale | Standard Error 0.54 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain at its Worst in Last 24 hours | -0.02 score on a scale | Standard Error 0.57 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered with Normal Work | 0.19 score on a scale | Standard Error 0.61 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain at its Least in Last 24 hours | 0.39 score on a scale | Standard Error 0.51 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | Pain Interfered Enjoyment of Life | -0.13 score on a scale | Standard Error 0.75 |
Comparison: Pain at its Worst in Last 24 Hoursp-value: 0.38395% CI: [-0.84, 2.13]Mixed Models Analysis
Comparison: Pain at its Worst in Last 24 Hoursp-value: 0.69295% CI: [-1.91, 1.28]Mixed Models Analysis
Comparison: Pain at its Least in Last 24 Hoursp-value: 0.46995% CI: [-0.85, 1.8]Mixed Models Analysis
Comparison: Pain at its Least in Last 24 Hoursp-value: 0.77695% CI: [-1.62, 1.22]Mixed Models Analysis
Comparison: Pain on the Averagep-value: 0.32895% CI: [-0.72, 2.11]Mixed Models Analysis
Comparison: Pain on the Averagep-value: 0.95495% CI: [-1.45, 1.54]Mixed Models Analysis
Comparison: Pain Right Nowp-value: 0.3595% CI: [-0.85, 2.36]Mixed Models Analysis
Comparison: Pain right now.p-value: 0.40595% CI: [-1.01, 2.44]Mixed Models Analysis
Comparison: Pain Interfered General Activityp-value: 0.56595% CI: [-1.06, 1.91]Mixed Models Analysis
Comparison: Pain Interfered General Activityp-value: 0.84895% CI: [-1.74, 1.43]Mixed Models Analysis
Comparison: Pain Interfered with Moodp-value: 0.92895% CI: [-1.37, 1.25]Mixed Models Analysis
Comparison: Pain Interfered with Moodp-value: 0.6595% CI: [-1.71, 1.08]Mixed Models Analysis
Comparison: Pain Interfered Walking Abilityp-value: 0.86595% CI: [-1.89, 1.6]Mixed Models Analysis
Comparison: Pain Interfered Walking Abilityp-value: 0.49795% CI: [-1.23, 2.5]Mixed Models Analysis
Comparison: Pain Interfered with Normal Workp-value: 0.27295% CI: [-0.72, 2.5]Mixed Models Analysis
Comparison: Pain Interfered with Normal Workp-value: 0.58395% CI: [-1.25, 2.19]Mixed Models Analysis
Comparison: Pain Interfered with Relationsp-value: 0.87695% CI: [-1.53, 1.79]Mixed Models Analysis
Comparison: Pain Interfered with relations.p-value: 0.64495% CI: [-1.37, 2.19]Mixed Models Analysis
Comparison: Pain Interfered with Sleepp-value: 0.38495% CI: [-0.97, 2.48]Mixed Models Analysis
p-value: 0.31895% CI: [-0.9, 2.71]Mixed Models Analysis
Comparison: Pain Interfered Enjoyment of Lifep-value: 0.40795% CI: [-1.15, 2.78]Mixed Models Analysis
Comparison: Pain Interfered Enjoyment of Lifep-value: 0.6295% CI: [-1.58, 2.62]Mixed Models Analysis
Comparison: BPI-Mean Interference Scorep-value: 0.47595% CI: [-0.9, 1.91]Mixed Models Analysis
Comparison: BPI-Mean Interference Scorep-value: 0.5495% CI: [-1.04, 1.96]Mixed Models Analysis
Secondary
Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: 1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). 2. Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much) 3. Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time frame: Baseline, 6 Months
Population: All randomized participants with baseline \& post baseline value for the EORTC QLQ-C30 specified item.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scale: Social Functioning | -21.12 units on a scale | Standard Error 4.9 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Role Functioning | -17.09 units on a scale | Standard Error 6.17 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Insomnia | -5.19 units on a scale | Standard Error 5.17 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Fatigue | 14.13 units on a scale | Standard Error 4.92 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Physical Functioning | -14.44 units on a scale | Standard Error 4.4 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Dysopnea | 0.35 units on a scale | Standard Error 5.48 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Nausea and Vomiting | 7.98 units on a scale | Standard Error 5.57 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Constipation | 2.96 units on a scale | Standard Error 5.95 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Pain | 9.79 units on a scale | Standard Error 5.63 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Emotional Functioning | -4.89 units on a scale | Standard Error 4.49 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Financial difficulties | 3.96 units on a scale | Standard Error 4.82 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Global Health Status | -6.21 units on a scale | Standard Error 3.87 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Cognitive Functioning | -10.43 units on a scale | Standard Error 4.1 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Diarrhoea | 15.71 units on a scale | Standard Error 6.76 |
| 200mg Abemaciclib | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Appetite Loss | 12.54 units on a scale | Standard Error 5.79 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Appetite Loss | 15.32 units on a scale | Standard Error 6.77 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Global Health Status | -4.82 units on a scale | Standard Error 4.5 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Physical Functioning | -11.65 units on a scale | Standard Error 5.12 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Role Functioning | -18.05 units on a scale | Standard Error 7.32 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Emotional Functioning | -0.63 units on a scale | Standard Error 5.22 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Cognitive Functioning | -8.39 units on a scale | Standard Error 4.77 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scale: Social Functioning | -17.09 units on a scale | Standard Error 5.72 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Fatigue | 14.90 units on a scale | Standard Error 5.73 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Nausea and Vomiting | 9.42 units on a scale | Standard Error 6.47 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Pain | 2.68 units on a scale | Standard Error 6.61 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Dysopnea | 11.19 units on a scale | Standard Error 6.38 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Insomnia | 1.83 units on a scale | Standard Error 6.01 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Constipation | -6.51 units on a scale | Standard Error 6.96 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Diarrhoea | 26.28 units on a scale | Standard Error 7.83 |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Financial difficulties | 2.45 units on a scale | Standard Error 5.68 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scale: Social Functioning | -2.00 units on a scale | Standard Error 5.95 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Diarrhoea | 20.51 units on a scale | Standard Error 7.98 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Insomnia | -6.71 units on a scale | Standard Error 6.05 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Cognitive Functioning | -5.18 units on a scale | Standard Error 4.95 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Emotional Functioning | 2.06 units on a scale | Standard Error 5.41 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Appetite Loss | 9.51 units on a scale | Standard Error 7.3 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Role Functioning | -17.10 units on a scale | Standard Error 7.36 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Global Health Status | -2.40 units on a scale | Standard Error 4.64 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Constipation | 12.93 units on a scale | Standard Error 7.15 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Nausea and Vomiting | 11.88 units on a scale | Standard Error 6.5 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Functional Scales: Physical Functioning | -5.42 units on a scale | Standard Error 5.12 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Pain | 5.43 units on a scale | Standard Error 6.62 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scales: Fatigue | 5.64 units on a scale | Standard Error 5.71 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Financial difficulties | -3.30 units on a scale | Standard Error 5.87 |
| Gemcitabine or Capecitabine | Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Symptom Scale: Dysopnea | -4.51 units on a scale | Standard Error 6.36 |
Comparison: Global health statusp-value: 0.81895% CI: [-13.46, 10.68]Mixed Models Analysis
Comparison: Global health statusp-value: 0.53395% CI: [-16.03, 8.42]Mixed Models Analysis
Comparison: Functional Scales: Physical functioningp-value: 0.68195% CI: [-16.4, 10.82]Mixed Models Analysis
Comparison: Functional Scales: Physical functioningp-value: 0.18995% CI: [-22.63, 4.59]Mixed Models Analysis
Comparison: Functional Scales: Role functioningp-value: 0.92195% CI: [-18.29, 20.21]Mixed Models Analysis
Comparison: Functional Scales: Role functioning.p-value: 0.99995% CI: [-19.4, 19.42]Mixed Models Analysis
Comparison: Functional Scales: Emotional functioningp-value: 0.54195% CI: [-18.2, 9.68]Mixed Models Analysis
Comparison: Functional Scales: Emotional functioningp-value: 0.3395% CI: [-21.17, 7.27]Mixed Models Analysis
Comparison: Functional Scales: Cognitive Functioningp-value: 0.74795% CI: [-14.74, 10.66]Mixed Models Analysis
Comparison: Functional Scales: Cognitive functioningp-value: 0.41995% CI: [-18.22, 7.73]Mixed Models Analysis
Comparison: Functional Scales: Social functioningp-value: 0.59695% CI: [-19.23, 11.19]Mixed Models Analysis
Comparison: Functional Scales: Social functioningp-value: 0.01795% CI: [-34.68, -3.55]Mixed Models Analysis
Comparison: Symptoms Scales: Fatiguep-value: 0.91995% CI: [-16.03, 14.49]Mixed Models Analysis
Comparison: Symptom Scales: Fatiguep-value: 0.26795% CI: [-6.72, 23.69]Mixed Models Analysis
Comparison: Symptom Scales: Nausea and Vomitingp-value: 0.86695% CI: [-18.66, 15.77]Mixed Models Analysis
Comparison: Symptom Scales: Nausea and Vomitingp-value: 0.65295% CI: [-21.23, 13.43]Mixed Models Analysis
Comparison: Symptom Scales: Painp-value: 0.41795% CI: [-10.39, 24.6]Mixed Models Analysis
Comparison: Symptom Scales: Painp-value: 0.61895% CI: [-13.16, 21.89]Mixed Models Analysis
Comparison: Symptom Scales: Dyspnoeap-value: 0.20695% CI: [-27.85, 6.18]Mixed Models Analysis
Comparison: Symptom Scales: Dyspnoeap-value: 0.56695% CI: [-12.08, 21.8]Mixed Models Analysis
Comparison: Symptom Scales: Insomniap-value: 0.3895% CI: [-23.01, 8.96]Mixed Models Analysis
Comparison: Symptom Scales: Insomniap-value: 0.8595% CI: [-14.6, 17.64]Mixed Models Analysis
Comparison: Symptom Scales: Appetite lossp-value: 0.75695% CI: [-20.78, 15.21]Mixed Models Analysis
Comparison: Symptom Scales: Appetite lossp-value: 0.74795% CI: [-15.77, 21.82]Mixed Models Analysis
Comparison: Symptom Scales: Constipationp-value: 0.31195% CI: [-9.16, 28.09]Mixed Models Analysis
Comparison: Symptom Scales: Constipationp-value: 0.2995% CI: [-28.75, 8.8]Mixed Models Analysis
Comparison: Symptom Scales: Diarrhoeap-value: 0.32395% CI: [-31.93, 10.78]Mixed Models Analysis
Comparison: Symptom Scales: Diarrhoeap-value: 0.65195% CI: [-26.08, 16.48]Mixed Models Analysis
Comparison: Symptom Scales: Financial Difficultiesp-value: 0.84195% CI: [-13.57, 16.59]Mixed Models Analysis
Comparison: Symptom Scales: Financial Difficultiesp-value: 0.34495% CI: [-8.03, 22.54]Mixed Models Analysis
Secondary
Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months
Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD ≥6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time frame: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200mg Abemaciclib | Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months | 3 percentage of participants |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months | 0 percentage of participants |
| Gemcitabine or Capecitabine | Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months | 3 percentage of participants |
p-value: 1Cochran-Mantel-Haenszel
p-value: 0.3017Cochran-Mantel-Haenszel
Secondary
Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD
Time frame: Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)
Population: Data not reported, no patients were enrolled to stage 2.
Secondary
Stage 2: Duration of Response (DoR)
Time frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months)
Population: The population for analyzing DoR is the number of participants with response of CR or PR. There was only one participant in 200 mg Abemaciclib arm and one participant in Gemcitabine/Capecitabine arm. Due to small number of participants, the data is not analyzable using the planned time to event analysis.
Secondary
Stage 2: Overall Survival (OS)
OS duration is measured from the date of randomization to the date of death from any cause. for participants who is not known to have died as of the data-inclusion cutoff date, OS was censored at the last known alive date. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time frame: Baseline to Death from Any Cause (Up to 10 Months)
Population: All randomized participants. Censored participants: Abemaciclib 200mg: 11, Abemaciclib 150mg + LY3023414 150mg: 12, Gemcitabine + Capecitabine: 21;
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 200mg Abemaciclib | Stage 2: Overall Survival (OS) | 2.71 Months |
| 150mg Abemaciclib + 150mg LY3023414 | Stage 2: Overall Survival (OS) | 3.29 Months |
| Gemcitabine or Capecitabine | Stage 2: Overall Survival (OS) | NA Months |
p-value: 0.193895% CI: [0.782, 3.272]Log Rank
p-value: 0.247795% CI: [0.746, 3.15]Log Rank