NCT00451555

Enzastaurin Plus Fulvestrant vs. Placebo Plus Fulvestrant in Breast Cancer

Completed Phase 2 Results posted Last updated 1 November 2019

What this trial tests

Phase 2 trial testing enzastaurin in Breast Cancer in 156 participants. Completed in 18 October 2018.

Timeline

11 April 2007

Primary endpoint
28 December 2010

18 October 2018

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	156
Start date	11 April 2007
Primary completion	28 December 2010
Estimated completion	18 October 2018
Sites	21 locations across France, Italy, Netherlands, Germany, Spain

Drugs / interventions tested

• enzastaurin — full drug profile →
• placebo
• fulvestrant (fulvestrant) — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieved a Best Response of Complete Response, Partial Response, and Stable Disease (CR+PR+SD) (Clinical Benefit Rate) Primary · Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

Clinical benefit rate is defined as the rate of confirmed CR, confirmed PR, and SD for 24 weeks duration and is the best response CR, PR, or SD as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for pr

Group	Value	95% CI
Enzastaurin + Fulvestrant QD + BID	43.6	33.4 – 54.2
Enzastaurin + Fulvestrant BID	43.6	27.8 – 60.4
Enzastaurin + Fulvestrant QD	43.6	30.3 – 57.7
Fulvestrant + Placebo	44.8	31.7 – 58.5

Percentage of Participants Achieving Overall Tumor Response Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR]) Secondary · Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

The ORR is equal to the percentage of participants achieving a best overall response of partial response or complete response (PR + CR), according to RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as having at least 20% increase in sum of longest diameter of target lesions and min

Group	Value	95% CI
Enzastaurin + Fulvestrant QD + BID	5.3	1.7 – 12.0
Enzastaurin + Fulvestrant BID	5.1	0.6 – 17.3
Enzastaurin + Fulvestrant QD	5.5	1.1 – 15.1
Fulvestrant + Placebo	5.2	1.1 – 14.4

Duration of Clinical Benefit Secondary · Time of Clinical Benefit to Progressive Disease or Death (Up to 3 Years)

The duration of clinical benefit was measured from the time of clinical benefit of CR, PR or SD to the time of progressive disease or death from any cause. PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints.

Group	Value	95% CI
Enzastaurin + Fulvestrant BID + QD	9.6	8.2 – 11.0
Enzastaurin + Fulvestrant BID	9.4	7.4 – 12.2
Enzastaurin + Fulvestrant QD	9.6	7.9 – 11.1
Placebo + Fulvestrant BID	9.7	7.4 – 12.6

Progression Free Survival (PFS) Secondary · Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 3 Years)

Progression-free survival (PFS) time was defined as the time from baseline to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir.For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summar

Group	Value	95% CI
Enzastaurin + Fulvestrant QD + BID	5.2	3.5 – 7.4
Enzastaurin + Fulvestrant BID	3.7	2.8 – 7.4
Enzastaurin + Fulvestrant QD	6.0	2.8 – 7.9
Fulvestrant + Placebo	5.5	3.8 – 7.4

Number of Participants Who Discontinued With Adverse Events (AE) and Serious Adverse Events (SAEs) Secondary · From Baseline to Study Completion (Up to 3 years, 9 months)

Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs, regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. Participants who discontinued due to an AE or SAE are reported.

Adverse Events (AEs)

Group	Value	95% CI
Enzastaurin + Fulvestrant QD + BID	3
Enzastaurin + Fulvestrant BID	1
Enzastaurin + Fulvestrant QD	2
Fulvestrant + Placebo	1

Serious Adverse Events (SAEs)

Group	Value	95% CI
Enzastaurin + Fulvestrant QD + BID	0
Enzastaurin + Fulvestrant BID	0
Enzastaurin + Fulvestrant QD	0
Fulvestrant + Placebo	1

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline to Study Completion (Up to 3 Years, 9 Months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fulvestrant + Enzastaurin (QD + BID)

Serious: 17/94 (18%)

Deaths: —

Fulvestrant + Enzastuarin (QD)

Serious: 9/39 (23%)

Deaths: —

Fulvestrant + Enzastuarin (BID)

Serious: 8/55 (15%)

Deaths: —

Fulvestrant + Placebo

Serious: 11/58 (19%)

Deaths: —

Serious adverse events (32 terms)

Reaction	System	Fulvestrant + Enzastaurin …	Fulvestrant + Enzastuarin …	Fulvestrant + Enzastuarin …	Fulvestrant + Placebo
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Ischaemic cardiomyopathy	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—
Ileus	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Disease progression	General disorders	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—	—	—
Hypersensitivity	Immune system disorders	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Femoral neck fracture	Injury, poisoning and procedural complications	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—
Leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Metastases to skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—

Other adverse events (53 terms — click to expand)

Reaction	System	Fulvestrant + Enzastaurin …	Fulvestrant + Enzastuarin …	Fulvestrant + Enzastuarin …	Fulvestrant + Placebo
Nausea	Gastrointestinal disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Hot flush	Vascular disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Chromaturia	Renal and urinary disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Cystitis	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Influenza like illness	General disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Infection	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—
Dysphonia	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—
Faeces discoloured	Gastrointestinal disorders	—	—	—	—

Most-reported serious reactions: Anaemia, Pleural effusion, Lymphadenopathy, Angina pectoris, Ischaemic cardiomyopathy, Myocardial infarction, Haemorrhoids, Ileus.

Data from ClinicalTrials.gov NCT00451555 adverse events section.

Sponsor's own description

The primary purpose of this study is to help answer the following research question: whether enzastaurin given together with fulvestrant can help participants who have breast cancer and make the tumor smaller or disappear and for how long.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.