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Study of Enzastaurin Versus Placebo in the Treatment of Patients With Brain Metastases of Lung Cancer, After Whole Brain Radiation Therapy

Primary Purpose

Non Small Cell Lung Cancer, Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
enzastaurin
placebo
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Having radiologically proven brain metastases of lung cancer
  • Having received whole brain radiotherapy with either 30 grays in 2 weeks or 20 grays in one week. Treatment with enzastaurin must start within 14 days after the last fraction of the whole brain radiotherapy
  • No other previous radiotherapy to the brain except for radiosurgery at one occasion
  • Adequate organ function as measured by appropriate laboratory tests.
  • Age 18 years or older.

Exclusion Criteria:

  • Inability to swallow tablets or show conditions which could interfere with oral medication intake (e.g. vomiting, partial bowel obstruction).
  • Inability to discontinue use of certain anti-epileptic drugs such as, carbamazepine, phenobarbital or phenytoin.
  • Concurrent administration of warfarin
  • Hemophilia
  • Having had any systemic anti-cancer treatment within the last 2 weeks prior to enrolment.

Sites / Locations

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

A

B

Arm Description

Outcomes

Primary Outcome Measures

Time to Progression of Brain Metastases
Time to progression (TTP) of brain metastases is the time from randomization to first observation of brain metastases progression. Response Evaluation Criteria In Solid Tumors (RECIST; Version 1.0), using magnetic resonance imaging (MRI), until observation of objective progression, or clinically as the date of increased steroids dose (barring radiological confirmation), was used to assess progressive disease (PD) of brain metastases. TTP was right-censored with the date of last contact if the participant died without MRI-documented PD or symptomatic deterioration or was lost to follow-up or received post therapy (Radio, Systemic, Surgery) before documented PD of the brain metastases.

Secondary Outcome Measures

Time to Objective Progression of Brain Metastases
Time to objective progression (TTOP) of brain metastases is the time from randomization to the first observation of objective progression of brain metastases assessed by MRI. TTOP was right-censored with the date of the last objective progression-free disease assessment if the participant died or did not have objective PD as of the cut-off date. For participants receiving post-discontinuation therapy prior to PD of brain metastases, TTOP was censored at the last assessment before post-discontinuation therapy. Kaplan-Meier estimated the median survival times and confidence intervals.
Overall Progression-free Survival (Including Both Progression of Brain and Extracranial Tumor Lesion)
Overall progression-free survival (PFS) is defined as the time from the date of study enrollment to the first date of progressive disease or death from any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at last contact date. For those who received subsequent systemic anticancer therapy (after discontinuation from study therapy) prior to objectively determined progression of brain metastases, PFS was censored at the start of radiotherapy for extracranial lesions or the date of starting chemotherapy.
Overall Survival
Overall survival (OS) was defined as the time from randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS was censored at the last contact date.
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Overall Response (OR) was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). OR on extra-cranial tumors was assessed by response sequences. Complete response (CR) or partial response (PR), was confirmed by second assessment performed >= 28 days after first response. Two CRs before progression required for best response of CR. Two PRs or better not qualifying for a CR, for best response of PR. CR: Disappearance of all tumor lesions. PR: 30% decrease from baseline in sum of the longest diameter of target lesions or complete disappearance of target lesions, without worsening of one or more nontarget lesions. In either case, no new lesions may have appeared. Stable Disease (SD) is defined as disease that does not meet the criteria for CR, PR, or progressive disease (PD), and has been evaluated at least 1 time, at least 6 weeks after baseline assessment.
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Best overall tumor response on brain metastases (BOR) according to RECIST V1.0 response criteria. For complete response (CR) or partial response (PR), BOR was to be confirmed. Response criteria were CR: Disappearance of all tumor lesions. PR: Either a) at least a 30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LDs or b) complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions. In either case, no new lesions may have appeared. Stable Disease (SD) is defined as disease that does not meet the criteria for CR, PR, or progressive disease (PD), and has been evaluated at least 1 time, at least 6 weeks after baseline assessment.
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Physical functioning was measured by items 1 to 5. Their sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better).
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100 (lower score is better).
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100 (lower score is better).
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100 (lower score is better).
HRQoL Questionnaire - QLQ-BN20 Headache
Health-related quality of life is measured using an EORTC quality of life questionnaire designed specifically for participants with brain tumors (BN-20). Questionnaires may be completed by the participant or with the assistance of the examiner at baseline prior to initiation of study therapy, and then approximately every 8 weeks while on study treatment (prior to discussing treatment response at each visit, whenever possible). All single questions are answered using a categorical scale (e.g., 1 = not at all; 2 = a little; 3 = quite a bit; 4 = very much) and linearly transformed to 0 to 100 scales with 1) higher scores for a functional scale representing higher levels of functioning, 2) higher scores for the global health status/quality of life representing higher levels of global health status/quality of life, 3) and higher scores for a symptom scale representing higher level of symptoms. For Headache lower score is better.
Number of Participants With Adverse Events
A summary of serious adverse events (SAEs) and all other non-serious adverse events is located in the Reported Adverse Event Module.

Full Information

First Posted
December 20, 2006
Last Updated
October 9, 2020
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00415363
Brief Title
Study of Enzastaurin Versus Placebo in the Treatment of Patients With Brain Metastases of Lung Cancer, After Whole Brain Radiation Therapy
Official Title
A Double-blind, Randomized, Placebo-controlled Multicentre Phase II Study of Maintenance Enzastaurin Following Whole Brain Radiation Therapy in the Treatment of Brain Metastases From Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is a multinational study to compare enzastaurin versus placebo in the treatment of patients with brain metastases of lung cancer. Approximately 108 patients will be randomly assigned to receive either enzastaurin or placebo after having completed whole brain radiotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
109 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Title
B
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
enzastaurin
Other Intervention Name(s)
LY317615
Intervention Description
1125 mg loading dose then 500 mg, oral, daily, until disease progression
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
oral, daily
Primary Outcome Measure Information:
Title
Time to Progression of Brain Metastases
Description
Time to progression (TTP) of brain metastases is the time from randomization to first observation of brain metastases progression. Response Evaluation Criteria In Solid Tumors (RECIST; Version 1.0), using magnetic resonance imaging (MRI), until observation of objective progression, or clinically as the date of increased steroids dose (barring radiological confirmation), was used to assess progressive disease (PD) of brain metastases. TTP was right-censored with the date of last contact if the participant died without MRI-documented PD or symptomatic deterioration or was lost to follow-up or received post therapy (Radio, Systemic, Surgery) before documented PD of the brain metastases.
Time Frame
Baseline to measured progressive disease (up to 21.2 months)
Secondary Outcome Measure Information:
Title
Time to Objective Progression of Brain Metastases
Description
Time to objective progression (TTOP) of brain metastases is the time from randomization to the first observation of objective progression of brain metastases assessed by MRI. TTOP was right-censored with the date of the last objective progression-free disease assessment if the participant died or did not have objective PD as of the cut-off date. For participants receiving post-discontinuation therapy prior to PD of brain metastases, TTOP was censored at the last assessment before post-discontinuation therapy. Kaplan-Meier estimated the median survival times and confidence intervals.
Time Frame
Baseline to measured progressive disease (up to 21.2 months)
Title
Overall Progression-free Survival (Including Both Progression of Brain and Extracranial Tumor Lesion)
Description
Overall progression-free survival (PFS) is defined as the time from the date of study enrollment to the first date of progressive disease or death from any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at last contact date. For those who received subsequent systemic anticancer therapy (after discontinuation from study therapy) prior to objectively determined progression of brain metastases, PFS was censored at the start of radiotherapy for extracranial lesions or the date of starting chemotherapy.
Time Frame
Baseline to measured progressive disease (up to 14.4 months)
Title
Overall Survival
Description
Overall survival (OS) was defined as the time from randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS was censored at the last contact date.
Time Frame
Baseline to date of death from any cause (up to 27.2 months)
Title
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Description
Overall Response (OR) was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). OR on extra-cranial tumors was assessed by response sequences. Complete response (CR) or partial response (PR), was confirmed by second assessment performed >= 28 days after first response. Two CRs before progression required for best response of CR. Two PRs or better not qualifying for a CR, for best response of PR. CR: Disappearance of all tumor lesions. PR: 30% decrease from baseline in sum of the longest diameter of target lesions or complete disappearance of target lesions, without worsening of one or more nontarget lesions. In either case, no new lesions may have appeared. Stable Disease (SD) is defined as disease that does not meet the criteria for CR, PR, or progressive disease (PD), and has been evaluated at least 1 time, at least 6 weeks after baseline assessment.
Time Frame
Baseline to measured progressive disease (up to 27.2 months)
Title
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Description
Best overall tumor response on brain metastases (BOR) according to RECIST V1.0 response criteria. For complete response (CR) or partial response (PR), BOR was to be confirmed. Response criteria were CR: Disappearance of all tumor lesions. PR: Either a) at least a 30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LDs or b) complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions. In either case, no new lesions may have appeared. Stable Disease (SD) is defined as disease that does not meet the criteria for CR, PR, or progressive disease (PD), and has been evaluated at least 1 time, at least 6 weeks after baseline assessment.
Time Frame
Baseline to measured progressive disease (up to 21.2 months)
Title
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Description
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Physical functioning was measured by items 1 to 5. Their sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better).
Time Frame
Baseline to 30 days after discontinuation (up to 17.6 months)
Title
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Description
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100 (lower score is better).
Time Frame
Baseline to 30 days after discontinuation (up to 17.6 months)
Title
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Description
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100 (lower score is better).
Time Frame
Baseline to 30 days after discontinuation (up to 17.6 months)
Title
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Description
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100 (lower score is better).
Time Frame
Baseline to 30 days after discontinuation (up to 17.6 months)
Title
HRQoL Questionnaire - QLQ-BN20 Headache
Description
Health-related quality of life is measured using an EORTC quality of life questionnaire designed specifically for participants with brain tumors (BN-20). Questionnaires may be completed by the participant or with the assistance of the examiner at baseline prior to initiation of study therapy, and then approximately every 8 weeks while on study treatment (prior to discussing treatment response at each visit, whenever possible). All single questions are answered using a categorical scale (e.g., 1 = not at all; 2 = a little; 3 = quite a bit; 4 = very much) and linearly transformed to 0 to 100 scales with 1) higher scores for a functional scale representing higher levels of functioning, 2) higher scores for the global health status/quality of life representing higher levels of global health status/quality of life, 3) and higher scores for a symptom scale representing higher level of symptoms. For Headache lower score is better.
Time Frame
Baseline to 30 days after discontinuation (up to 17.6 months)
Title
Number of Participants With Adverse Events
Description
A summary of serious adverse events (SAEs) and all other non-serious adverse events is located in the Reported Adverse Event Module.
Time Frame
every 6 weeks (up to 27.2 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Having radiologically proven brain metastases of lung cancer Having received whole brain radiotherapy with either 30 grays in 2 weeks or 20 grays in one week. Treatment with enzastaurin must start within 14 days after the last fraction of the whole brain radiotherapy No other previous radiotherapy to the brain except for radiosurgery at one occasion Adequate organ function as measured by appropriate laboratory tests. Age 18 years or older. Exclusion Criteria: Inability to swallow tablets or show conditions which could interfere with oral medication intake (e.g. vomiting, partial bowel obstruction). Inability to discontinue use of certain anti-epileptic drugs such as, carbamazepine, phenobarbital or phenytoin. Concurrent administration of warfarin Hemophilia Having had any systemic anti-cancer treatment within the last 2 weeks prior to enrolment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours,, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Kobenhavn
ZIP/Postal Code
2100
Country
Denmark
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Trondheim
ZIP/Postal Code
7006
Country
Norway
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Olsztyn
ZIP/Postal Code
10-228
Country
Poland
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Cluj-Napoca
ZIP/Postal Code
3400
Country
Romania
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Gothenburg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Umea
ZIP/Postal Code
90185
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

Study of Enzastaurin Versus Placebo in the Treatment of Patients With Brain Metastases of Lung Cancer, After Whole Brain Radiation Therapy

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