Trial Outcomes & Findings for A Study of Enzastaurin in Participants With Follicular Lymphoma (NCT NCT00475644)
NCT ID: NCT00475644
Last Updated: 2018-11-05
Results Overview
Tumor response rate is defined as the number of responders divided by the number of treated patients. A responder is a patient who exhibits a complete response (CR), complete response unconfirmed (CRu), or partial response (PR) as defined by Cheson et al. CR, the disappearance of target lesions and any pathological lymph nodes \[target or non-target\] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.
COMPLETED
PHASE2
66 participants
Baseline to Measured Progressive Disease (up to 1559 Days)
2018-11-05
Participant Flow
Participants who were considered to have completed the study who received at least 1 dose of study drug, did not have any protocol violations, and from whom a valid assay result was obtained.
Participant milestones
| Measure |
Enzastaurin
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Overall Study
STARTED
|
66
|
|
Overall Study
Received at Least One Dose of Study Drug
|
66
|
|
Overall Study
COMPLETED
|
53
|
|
Overall Study
NOT COMPLETED
|
13
|
Reasons for withdrawal
| Measure |
Enzastaurin
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Overall Study
Protocol Violation
|
13
|
Baseline Characteristics
A Study of Enzastaurin in Participants With Follicular Lymphoma
Baseline characteristics by cohort
| Measure |
Enzastaurin
n=66 Participants
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Age, Continuous
|
60.55 years
STANDARD_DEVIATION 11.851 • n=5 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
63 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
61 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Measured Progressive Disease (up to 1559 Days)Population: Participants who received at least 1 dose of study drug and did not violate any study criteria.
Tumor response rate is defined as the number of responders divided by the number of treated patients. A responder is a patient who exhibits a complete response (CR), complete response unconfirmed (CRu), or partial response (PR) as defined by Cheson et al. CR, the disappearance of target lesions and any pathological lymph nodes \[target or non-target\] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.
Outcome measures
| Measure |
Enzastaurin
n=53 Participants
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Tumor Response Rate (RR) (Percentage of Participants Exhibiting Complete Response [CR] or Complete Response Unconfirmed [CRu] or Partial Response [PR])
|
26.4 percentage of participants
Interval 15.3 to 40.3
|
SECONDARY outcome
Timeframe: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 1559 Days)Population: Participants who received at least 1 dose of study drug and who did not violate any study entry criteria. There were 18 censored participants.
PFS is defined as the time from the date of study enrollment to the first date of measured progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy. For reference, PFS will also be calculated and analyzed based on an alternative definition of censoring: for each patient who is not known to have died or to have had objective progression of disease as of the data cut-off date, PFS will be censored for that analysis at the date of last prior contact.
Outcome measures
| Measure |
Enzastaurin
n=53 Participants
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Progression-Free Survival (PFS)
|
551.0 Days
Interval 350.0 to 863.0
|
SECONDARY outcome
Timeframe: Baseline to Date of Confirmed Response (Up to 890 Days)Population: Participants who received at least 1 dose of study drug and did not violate any study entry criteria and who had baseline and post-baseline response data.
TtR is defined as the time from the date of study enrollment to the date of response (CR, CRu, or PR) for patients who have responded prior to receiving any subsequent anticancer therapy.CR, the disappearance of target lesions and any pathological lymph nodes \[target or non-target\] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.
Outcome measures
| Measure |
Enzastaurin
n=14 Participants
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Time to Response (TtR)
|
148.0 Days
Interval 84.0 to 246.0
|
SECONDARY outcome
Timeframe: Time of Response to Measured Progressive Disease (Up to 1415 Days)Population: Participants who received at least 1 dose of study drug, did not violate any study entry criteria and had baseline and post-baseline response data. There were 4 censored participants.
DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease), DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date. For responding participants who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression, DoR will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy.
Outcome measures
| Measure |
Enzastaurin
n=14 Participants
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Duration of Response (DoR)
|
677.5 Days
Interval 269.0 to
Data is not available to be presented because endpoint was not reached.
|
SECONDARY outcome
Timeframe: BaselinePopulation: The TR (Translational Research) population consisted of participants from whom tumor tissue was obtained.
Correlative analyses of tumor RR for PKC-β2 (protein kinase C-β) protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm reported as H scores (logistic model of response rate), which was derived from a weighted average of staining intensity (scale 0 to 3, increasing intensity) and percentage of positive cells (0 to 100%) at each staining intensity. PKC-β2 expression was further classified into high vs. low expression using the cutpoint of the median of the distribution of PKC-β2 H scores.
Outcome measures
| Measure |
Enzastaurin
n=12 Participants
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Number of Participants With Response With Expression of Protein Biomarkers
High Expression
|
1 participants
|
|
Number of Participants With Response With Expression of Protein Biomarkers
Low Expression
|
5 participants
|
Adverse Events
Enzastaurin
Serious adverse events
| Measure |
Enzastaurin
n=66 participants at risk
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Cardiac disorders
Angina pectoris
|
1.5%
1/66 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
1.5%
1/66 • Number of events 1
|
|
Eye disorders
Visual acuity reduced
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
1.5%
1/66 • Number of events 2
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Pancreatitis
|
1.5%
1/66 • Number of events 1
|
|
Gastrointestinal disorders
Pancreatitis acute
|
1.5%
1/66 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
1.5%
1/66 • Number of events 1
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.5%
1/66 • Number of events 2
|
|
Infections and infestations
Bronchitis
|
1.5%
1/66 • Number of events 1
|
|
Infections and infestations
Sepsis
|
1.5%
1/66 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.5%
1/66 • Number of events 6
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.5%
1/66 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fractured sacrum
|
1.5%
1/66 • Number of events 2
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
1.5%
1/66 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
1.5%
1/66 • Number of events 1
|
|
Metabolism and nutrition disorders
Failure to thrive
|
1.5%
1/66 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
1.5%
1/66 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.5%
1/66 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.5%
1/66 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
4.3%
1/23 • Number of events 3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal adenoma
|
1.5%
1/66 • Number of events 1
|
|
Psychiatric disorders
Mental status changes
|
1.5%
1/66 • Number of events 1
|
|
Renal and urinary disorders
Renal mass
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.5%
1/66 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.5%
1/66 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
1.5%
1/66 • Number of events 1
|
Other adverse events
| Measure |
Enzastaurin
n=66 participants at risk
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.6%
9/66 • Number of events 36
|
|
Cardiac disorders
Palpitations
|
6.1%
4/66 • Number of events 19
|
|
Gastrointestinal disorders
Abdominal distension
|
10.6%
7/66 • Number of events 29
|
|
Gastrointestinal disorders
Abdominal pain
|
12.1%
8/66 • Number of events 22
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.6%
5/66 • Number of events 22
|
|
Gastrointestinal disorders
Constipation
|
15.2%
10/66 • Number of events 53
|
|
Gastrointestinal disorders
Diarrhoea
|
30.3%
20/66 • Number of events 121
|
|
Gastrointestinal disorders
Dyspepsia
|
9.1%
6/66 • Number of events 38
|
|
Gastrointestinal disorders
Faeces discoloured
|
15.2%
10/66 • Number of events 91
|
|
Gastrointestinal disorders
Flatulence
|
7.6%
5/66 • Number of events 21
|
|
Gastrointestinal disorders
Nausea
|
28.8%
19/66 • Number of events 77
|
|
Gastrointestinal disorders
Stomatitis
|
7.6%
5/66 • Number of events 12
|
|
Gastrointestinal disorders
Vomiting
|
7.6%
5/66 • Number of events 5
|
|
General disorders
Fatigue
|
37.9%
25/66 • Number of events 139
|
|
General disorders
Oedema peripheral
|
9.1%
6/66 • Number of events 26
|
|
Infections and infestations
Nasopharyngitis
|
6.1%
4/66 • Number of events 12
|
|
Infections and infestations
Oral herpes
|
6.1%
4/66 • Number of events 13
|
|
Infections and infestations
Rhinitis
|
6.1%
4/66 • Number of events 5
|
|
Infections and infestations
Sinusitis
|
7.6%
5/66 • Number of events 11
|
|
Infections and infestations
Upper respiratory tract infection
|
7.6%
5/66 • Number of events 10
|
|
Infections and infestations
Urinary tract infection
|
7.6%
5/66 • Number of events 6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.1%
4/66 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
11/66 • Number of events 56
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.6%
9/66 • Number of events 44
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.1%
4/66 • Number of events 22
|
|
Nervous system disorders
Dizziness
|
12.1%
8/66 • Number of events 50
|
|
Nervous system disorders
Headache
|
16.7%
11/66 • Number of events 69
|
|
Psychiatric disorders
Insomnia
|
7.6%
5/66 • Number of events 34
|
|
Renal and urinary disorders
Chromaturia
|
21.2%
14/66 • Number of events 114
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.7%
13/66 • Number of events 36
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.1%
8/66 • Number of events 43
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.1%
4/66 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.1%
4/66 • Number of events 26
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.1%
4/66 • Number of events 21
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
12.1%
8/66 • Number of events 36
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.1%
6/66 • Number of events 27
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
6.1%
4/66 • Number of events 10
|
Additional Information
Cheif Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60