A Non-Interventional Study With Aromasin® As Adjuvant Treatment Of Invasive Early Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01121549
• Collaborator: (none)
• Enrollment: 378
• Locations: 40
• Duration (Months): 34
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The IES study (A5991012) investigated 4742 patients treated for 2 to 3 years with tamoxifen, who either continued the same treatment or switched to Aromasin® for a total treatment period of 5 years. Only 65 Romanian patients were enrolled in the IES study. It would therefore appear to be essential to evaluate and confirm the tolerability of Aromasin® and the ways in which it is used on a broader sample of patients and under the standard conditions of use as stipulated in the MA. This Non-Interventional study was designed to address these issues.

Condition or Disease	Intervention/Treatment	Phase
Invasive Early Breast Cancer	Drug: Aromasin

Detailed Description

This is a prospective, non-comparative, non interventional study (NIS) in four hundred (400) postmenopausal women hormone-receptor positive invasive with early breast cancer, following 2-3 years of initial adjuvant tamoxifen therapy conducted in 60 sites from Romania according to protocol A5991091.The selection of patients based on diagnosis, the attribution of medicinal products and the follow-up of the subjects fall within the current medical practice. A Non-Interventional study is primarily observational in nature. The present Non-interventional Study is performed by medical oncologist and medical oncologist /radiation oncologist who agree to take part in this project. n/a The study was prematurely terminated on August 31th 2012 due to unexpected high rate of patient withdrawal caused by Aromasin reimbursement policy change in Romania; There were no safety issues related to study termination.

Study Design

• Study Type: Observational
• Actual Enrollment: 378 participants
• Time Perspective: Prospective
• Official Title: A Non-Interventional Study With Aromasin® As Adjuvant Treatment Of Invasive Early Breast Cancer In Postmenopausal Hormone Receptors Positive Patients Following Of 2-3 Years of Initial Adjuvant Tamoxifen Therapy
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Aromasin All patients included in the study	Drug: Aromasin; 25 mg daily continuously; Other Names: exemestane

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Baseline up to 28 days after last dose]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded using National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE,v4.0) as Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention; limiting age-appropriate instrumental activities of daily living [ADL]); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization; disabling; limiting self-care ADL); Grade 4 (Life-threatening; urgent intervention indicated) and Grade 5 (Death related to AE).

2. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug [Baseline up to 28 days after last dose]

   An AE (all causalities) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to exemestane was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

Secondary Outcome Measures

1. Number of Missed Exemestane Doses [Week 25, 49, 73, 97, 121, 145]

2. Number of Participants With Reasons for Discontinuing Exemestane Therapy [Baseline up to Year 3]

3. Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy [Baseline up to Year 3]

4. Percentage of Participants Who Discontinued the Exemestane Therapy [Baseline up to Year 3]

5. Recurrence-free Survival (RFS) [Baseline up to Year 3]

   Recurrence-free survival defined as the time from study inclusion to the first date of documented recurrence, with events defined as: local recurrence, distant recurrence, new primary breast cancer (includes both ipsilateral and contralateral second primaries), or death due to any cause. New primary cancer at sites other than the breast were not considered as recurrence.

6. Time to Disease Progression (TTP) [Baseline up to Year 3]

   Time to disease progression was defined as the time from inclusion to first local or distant recurrence at any site.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal females, defined as one from the next :

1. Natural menopause >/=1 year,

2. Surgical ovariectomy,

3. Chemotherapy-induced amenorrhoea >/=2 years.

• Patients who have had surgical treatment for histological confirmed breast cancer that was non-metastatic at the time of the initial diagnosis.

• Patients who are disease-free after 2 or 3 years of adjuvant tamoxifen treatment.

• Patients whose tumour was estrogen receptor positive (ER+).

• Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• Patients for whom Aromasin® treatment is contraindicated (see SmPC).

• Presence of metastasis or a contra lateral tumour.

• Other adjuvant endocrine therapy.

• Another concomitant antineoplastic treatment

• Participation in a clinical trial with an investigational drug during the 30 days prior to enrolment in the study.

• The patients are not supposed to participate to any other trial during all the study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Policlinica Judeteana 1 Pitesti - Cabinet oncologie	Pitesti	Arges	Romania	110084
2	Spitalul Judetean de Urgenta Resita Sectia oncologie medicala	Resita	Caras Severin	Romania	320076
3	Spitalul Clinic Judetean de Urgenta Cluj, Clinica de Oncologie Medicala si Radioterapie	Cluj Napoca	Cluj	Romania	40006
4	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj-Napoca	Cluj	Romania	400015
5	Spitalul Judetean Covasna, Sectia Oncologie medicala	Sfantu Gheorghe	Covasna	Romania	520064
6	Spitalul Judetean de Urgenta Targoviste	Targoviste	Dambovita	Romania	130095
7	Spital Clinic Judetean de Urgenta Oradea	Oradea	Jud. Bihor	Romania	410167
8	Spitalul Judeţean Brasov	Brasov	Jud. Brasov	Romania	505200
9	Spitalulul Judetean Clinic de Urgenta, Sf. Apostol Andrei	Galati	Jud. Galati	Romania	800367
10	Spitalul Judetean Bistrita Nasaud - Sectia Oncologie Medicala	Bistrita	Jud. Nasaud	Romania	420178
11	Spitalul Clinic Judetean de Urgenta Sibiu - Sectia Oncologie Medicala	Sibiu	Jud. Sibiu	Romania	550245
12	Spitalul Judetean Drobeta Turnu Severin - Sectie oncologie	Drobeta Turnu Severin	Mehedinti	Romania	220064
13	Spitalul Judetean Targu Mures	Targu Mures	Mures	Romania	540140
14	Spitalulul Municipal de Urgenta Roman	Roman	Neamt	Romania	617385
15	Spitalul Judetean de Urgenta Slatina, Sectie oncologie	Slatina	Olt	Romania	230008
16	Spitalul Municipal Campina Sectia oncologie	Campina	Prahova	Romania	107425
17	Spitalul Municipal Ploiesti Sectia oncologie	Ploiesti	Prahova	Romania	100337
18	Spitalul Municipal Medias Compartimentul Oncologie medicala	Medias	Sibiu	Romania	551026
19	Spitalul Clinic Municipal de Urgenta Timisoara Clinica Oncologie Medicala	Timisoara	Timis	Romania	300223
20	Spitalul Clinic Municipal Timisoara Sectia oncologie medicala	Timisoara	Timis	Romania	300223
21	Oncomed Srl	Timisoara	Timis	Romania	300239
22	Spitalul Judetean de Urgenta Bacau	Bacau		Romania	600114
23	Policlinica Theodor Burghele, cabinet oncologie	Bucharest		Romania	50659
24	Str. Povernei 42, Sector 1	Bucharest		Romania	7000
25	CMDT MAPN Washington Ambulator oncologie	Bucuresti		Romania	011794
26	Ambulator Spital Colentina, cabinet oncologie	Bucuresti		Romania	020142
27	Cabinet Oncologie Medicala	Bucuresti		Romania	020947
28	Ambulator Spital Sf. Pantelimon, cabinet oncolgie	Bucuresti		Romania	021659
29	Institutul Oncologic "Prof. Dr. Al. Trestioreanu"	Bucuresti		Romania	022328
30	Ambulator Spital Clinic Colţea, cabinet oncologie	Bucuresti		Romania	030171
31	Centru D.T. Titan Cabinet oncologie	Bucuresti		Romania	030442
32	Policlinica Sf. Ioan Bucuresti, cabinet oncologie	Bucuresti		Romania	042121
33	Ambulator Specialitate Cotroceni, cabinet oncolgie	Bucuresti		Romania	7000
34	Spitalulul Judetean de Urgenta Deva, Ambulator oncologie medicala	Hunedoara		Romania	331021
35	Spitalulul Clinic Judetean de Urgenta Sf. Spiridon, Ambulatoriu de specialitate adulti - Stationar o	Iasi		Romania	700106
36	Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi Clinica Oncologie Medicala	Iasi		Romania	700111
37	Spitalul Clinic de Urgenta	Oradea		Romania	410032
38	Spitalulul Clinic Judetean de Urgenta Sibiu- Sectia Oncologie medicala	Sibiu		Romania	550245
39	Spitalulul Judetean de Urgenta, Sf. Ioan cel Nou	Suceava		Romania	720131
40	Spitalul Judetean de Urgenta Targu Jiu, Ambulator Spital - Oncologie medicala	Targu Jiu		Romania	210140

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01121549
• Other Study ID Numbers: A5991091
• First Posted: May 12, 2010
• Last Update Posted: Jan 22, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Pfizer: Prospective; non-comparative; NIS; 600; postmenopausal; hormone-receptor; positive; EBC; tamoxifen; current medical practice.
• Additional relevant MeSH terms: Breast Neoplasms; Exemestane

Study Results

Participant Flow

Recruitment Details	All participants were recruited from Romania.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Period Title: Overall Study
STARTED	378
COMPLETED	31
NOT COMPLETED	347

Baseline Characteristics

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Overall Participants	378
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.3 (9.6)
Sex: Female, Male (Count of Participants)
Female	378 100%
Male	0 0%
Number of Participants With Type of Tumor (participants) [Number]
Ductal Carcinoma	58 15.3%
Lobular Carcinoma	4 1.1%
Invasive Ductal Carcinoma	246 65.1%
Invasive Lobular Carcinoma	22 5.8%
Papillary Carcinoma	2 0.5%
Medullary Carcinoma	1 0.3%
Mucinous (Colloid) Carcinoma	5 1.3%
Other	24 6.3%
Missing/No Response	16 4.2%
Number of Participants With Type of Surgery (participants) [Number]
Appendicectomy	6 1.6%
Breast lump removal	1 0.3%
Cataract operation	1 0.3%
Cholecystectomy	17 4.5%
Hysterectomy	3 0.8%
Intervertebral disc operation	1 0.3%
Malignant tumor excision	1 0.3%
Salpingo-oophorectomy bilateral	1 0.3%
Splenectomy	1 0.3%
Number of Participants With Estrogen Receptor Positive (participants) [Number]
Number [participants]	378 100%
Number of Participants With Lymph Node Involvement (participants) [Number]
Number [participants]	NA NaN
Number of Participants With Tumor Node Metastasis (TNM) Stage (participants) [Number]
Stage I	64 16.9%
Stage IIA	129 34.1%
Stage IIB	92 24.3%
Stage IIIA	67 17.7%
Stage IIIB	16 4.2%
Stage IIIC	2 0.5%
Other	2 0.5%
Missing/No Response	6 1.6%
Number of Participants With Histopathological Grade (participants) [Number]
Grade 1	62 16.4%
Grade 2	178 47.1%
Grade 3	65 17.2%
Unknown	70 18.5%
Missing/No Response	3 0.8%
Number of Participants With Prior Chemotherapy (participants) [Number]
Number [participants]	0 0%
Number of Participants With Prior Radiation Therapy (participants) [Number]
Number [participants]	239 63.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded using National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE,v4.0) as Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention; limiting age-appropriate instrumental activities of daily living [ADL]); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization; disabling; limiting self-care ADL); Grade 4 (Life-threatening; urgent intervention indicated) and Grade 5 (Death related to AE).
Time Frame	Baseline up to 28 days after last dose

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	378
Grade 1	6 1.6%
Grade 2	8 2.1%
Grade 3	6 1.6%
Grade 4	2 0.5%
Grade 5	0 0%
Missing or Unknown	2 0.5%

2. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug
Description	An AE (all causalities) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to exemestane was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
Time Frame	Baseline up to 28 days after last dose

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	378
AEs (All Causalities)	24 6.3%
SAEs (All Causalities)	5 1.3%
AEs (Treatment Related)	13 3.4%
SAEs (Treatment Related)	0 0%

3. Secondary Outcome

Title	Number of Missed Exemestane Doses
Time Frame	Week 25, 49, 73, 97, 121, 145

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who had received at least 1 dose of exemestane during the observation period. 'N' (number of participants analyzed)=participants evaluable for this measure. n=number of participants evaluable at specified time points. None of the participants were evaluable at Week 145 and hence data not reported.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	18
Week 25 (n=18)	4.9 (7.02)
Week 49 (n=8)	9.6 (20.40)
Week 73 (n=5)	7.6 (12.54)
Week 97 (n=4)	12.3 (13.07)
Week 121 (n=4)	6.3 (0.50)

4. Secondary Outcome

Title	Number of Participants With Reasons for Discontinuing Exemestane Therapy
Time Frame	Baseline up to Year 3

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	378
Adverse event	10 2.6%
Insufficient clinical response	11 2.9%
Did not meet entrance criteria	9 2.4%
Lost to follow-up	12 3.2%
No longer willing to participate in study	16 4.2%
Other unspecified	58 15.3%
Protocol violation	33 8.7%
Study terminated by sponsor	197 52.1%
Withdrawn due to pregnancy	1 0.3%

5. Secondary Outcome

Title	Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy
Time Frame	Baseline up to Year 3

Outcome Measure Data

Analysis Population Description

FAS included all participants who had received at least 1 dose of exemestane during the observation period.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	378
Received hormonal therapy	4 1.1%
Received chemotherapy	319 84.4%
Received both hormonal and chemotherapy	1 0.3%
No hormonal or chemotherapy received	34 9%
Missing or no response	20 5.3%

6. Secondary Outcome

Title	Percentage of Participants Who Discontinued the Exemestane Therapy
Time Frame	Baseline up to Year 3

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	378
Number [percentage of participants]	91.8 24.3%

7. Secondary Outcome

Title	Recurrence-free Survival (RFS)
Description	Recurrence-free survival defined as the time from study inclusion to the first date of documented recurrence, with events defined as: local recurrence, distant recurrence, new primary breast cancer (includes both ipsilateral and contralateral second primaries), or death due to any cause. New primary cancer at sites other than the breast were not considered as recurrence.
Time Frame	Baseline up to Year 3

Outcome Measure Data

Analysis Population Description

A subgroup of participants from FAS who had documented recurrence was evaluable for this measure.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	14
Median (Full Range) [weeks]	74.357

8. Secondary Outcome

Title	Time to Disease Progression (TTP)
Description	Time to disease progression was defined as the time from inclusion to first local or distant recurrence at any site.
Time Frame	Baseline up to Year 3

Outcome Measure Data

Analysis Population Description

Time to disease progression was considered complementary to RFS and hence, was not analyzed.

Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Exemestane
Arm/Group Description	Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy.
All Cause Mortality
	Exemestane
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Exemestane
	Affected / at Risk (%)	# Events
Total	5/378 (1.3%)
Cardiac disorders
Atrial fibrillation	1/378 (0.3%)
Eye disorders
Cataract	1/378 (0.3%)
Visual acuity reduced	1/378 (0.3%)
Gastrointestinal disorders
Intestinal obstruction	1/378 (0.3%)
Hepatobiliary disorders
Cholelithiasis	1/378 (0.3%)
Infections and infestations
Pyelonephritis acute	1/378 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer	1/378 (0.3%)
Meningioma	1/378 (0.3%)
Nervous system disorders
Cerebrovascular accident	1/378 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis	1/378 (0.3%)
Vascular disorders
Hypertensive crisis	1/378 (0.3%)
Other (Not Including Serious) Adverse Events
	Exemestane
	Affected / at Risk (%)	# Events
Total	5/378 (1.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/378 (1.3%)

Limitations/Caveats

The study was prematurely terminated on 31 August 2012 due to unexpected high rate of participant withdrawal caused by Aromasin reimbursement policy change in Romania. There were no safety issues related to study termination.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.