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

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00415363
• Other study ID #: 10710
• Secondary ID: H6Q-MC-S020
• Status: Completed
• Phase: Phase 2
• Start date: December 2006
• Est. completion date: January 2011

Study information

• Verified date: October 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non Small Cell Lung Cancer
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• enzastaurin
1125 mg loading dose then 500 mg, oral, daily, until disease progression
• placebo
oral, daily

Locations

Country	Name	City	State
Denmark	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.	Kobenhavn
Norway	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.	Bergen
Norway	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.	Trondheim
Poland	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.	Olsztyn
Romania	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.	Cluj-Napoca
Sweden	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.	Gothenburg
Sweden	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.	Umea

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Denmark,  Norway,  Poland,  Romania,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to measured progressive disease (up to 21.2 months)
Secondary	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.	Baseline to measured progressive disease (up to 21.2 months)
Secondary	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.	Baseline to measured progressive disease (up to 14.4 months)
Secondary	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.	Baseline to date of death from any cause (up to 27.2 months)
Secondary	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.	Baseline to measured progressive disease (up to 27.2 months)
Secondary	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.	Baseline to measured progressive disease (up to 21.2 months)
Secondary	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).	Baseline to 30 days after discontinuation (up to 17.6 months)
Secondary	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).	Baseline to 30 days after discontinuation (up to 17.6 months)
Secondary	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).	Baseline to 30 days after discontinuation (up to 17.6 months)
Secondary	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).	Baseline to 30 days after discontinuation (up to 17.6 months)
Secondary	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.	Baseline to 30 days after discontinuation (up to 17.6 months)
Secondary	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.	every 6 weeks (up to 27.2 months)

External Links

•   Lilly Clinical Trial Registry