Multicenter Follow Up Study Of Subjects Who Participated In An Original Protocol Of Exemestane Vs. Megestrol Acetate In Postmenopausal Women With Metastatic Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01237327
• Collaborator: (none)
• Enrollment: 84
• Locations: 7
• Arms: 2
• Duration (Months): 97
• Patients Per Site: 12
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Long term efficacy of exemestane as compared to megestrol acetate in the treatment of women with natural or induced postmenopausal status with advanced breast cancer whose disease has progressed following anti-estrogens or anti-estrogens plus chemotherapy and who had participated on an original study of exemestane vs megestrol : study 971-ONC-0028-080.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Megestrol acetate; Drug: exemestane (Aromasin)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Follow-up of the Study 971-ONC-0028-080: Exemestane Versus Megestrol Acetate In Postmenopausal Patients With Metastatic Breast Cancer, Failing Anti-Estrogens: An Open-Label, Randomized, Parallel-Group, Phase III Comparative Study
• Study Start Date: Nov 1, 2001
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: Megestrol acetate; Megestrol Acetate 160 mg oral tablets Qd; Other Names: Megace
Experimental: 2	Drug: exemestane (Aromasin); exemestane (Aromasin) 25 mg oral tablets Qd; Other Names: Aromasin

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Every 12 weeks up to 6 years]

   Overall survival in months measured from date of starting treatment in core study to date of death for any reason.

Secondary Outcome Measures

1. Objective Response Rate (ORR) [Every 12 weeks up to 6 years]

   Percentage of participants achieving an objective response (OR) defined as complete response (CR) or partial response (PR) out of the total number of participants randomized in each treatment group

2. Duration of Response (DR) [Every 12 weeks up to 6 years]

   Duration of objective response (complete response [CR] or partial response [PR]) calculated from date objective response was first documented to date of progressive disease. For subjects proceeding from PR to CR, the onset of PR was taken as the onset of objective response.

3. Time to Tumor Progression (TTP) [Every 12 weeks up to 6 years]

   TTP = time between first day of study treatment and date of documented disease progression, or date of tumor-related death in the absence of previously documented progressive disease (PD). PD defined as a 25% or greater increase in size of 1 or more lesions compared to smallest previous assessment, or appearance of new lesion, or unequivocal worsening of bone lesions, or progression of nonevaluable lesions.

4. Time to Treatment Failure (TTF) [Every 12 weeks up to 6 years]

   TTF = time between first day of study treatment and date of diagnosis of progression, withdrawal from study treatment for any reason, administration of other antitumor treatment, or death from any cause, whichever was the earliest event.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Previous participation in study 971-ONC-0028-080.

Exclusion Criteria:

• Subjects who had not previously participated in study 971-ONC-0028-080.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing		China	100021
2	PLA 307 Hospital	Beijing		China	100039
3	Ba Yi Hospital, Cancer Center of CPLA	Nanjing		China	210002
4	Jiangsu Cancer Hospital	Nanjing		China	210009
5	Cancer Hospital	Shanghai		China	200032
6	The 2nd Central Hospital of Tianjin	Tianjin		China	300120
7	The 1st Affiliated Hospital, Xi'an Jiao Tong University	Xi'an		China	710061

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.

• ClinicalTrials.gov Identifier: NCT01237327
• Other Study ID Numbers: 971-ONC-0028-094; A5991027
• First Posted: Nov 9, 2010
• Last Update Posted: May 6, 2011
• Last Verified: May 1, 2011

• Keywords provided by , ,: Metastatic Breast Cancer; Advanced; Postmenopausal; Exemestane vs Megestrol
• Additional relevant MeSH terms: Breast Neoplasms; Exemestane; Megestrol; Megestrol Acetate

Study Results

Participant Flow

Pre-assignment Detail	Follow-up study for participants in core study who completed 26 weeks of treatment, progressed while on therapy, or dropped out for any reason. Those who benefitted from core study treatment continued according to original randomization. Those who dropped out of core study received therapy appropriate for disease and were followed for survival.

Arm/Group Title	Exemestane	Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily
Period Title: Overall Study
STARTED	43	41
Stopped Treatment in Core Study (D/C)	22	24
Completed Treatment in Core Study	3	2
Continued Treatment in Extension Study	21	17
COMPLETED	1	1
NOT COMPLETED	42	40

Baseline Characteristics

Arm/Group Title	Exemestane	Megestrol Acetate	Total
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily	Total of all reporting groups
Overall Participants	43	41	84
Age, Customized (participants) [Number]
< 50 years	10 23.3%	15 36.6%	25 29.8%
50 to 64 years	17 39.5%	24 58.5%	41 48.8%
65 to 79 years	16 37.2%	2 4.9%	18 21.4%
Sex: Female, Male (Count of Participants)
Female	43 100%	41 100%	84 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival in months measured from date of starting treatment in core study to date of death for any reason.
Time Frame	Every 12 weeks up to 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT): participants randomized to study medication in core study who consented to participation in extension study.

Arm/Group Title	Exemestane	Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily
Measure Participants	43	41
Median (95% Confidence Interval) [months]	29.2	16.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Megestrol Acetate
	Comments	Overall survival compared using the hazard ratio; hazard ratio <1.0 is in favor of exemestane.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3348
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.7799
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.294
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Percentage of participants achieving an objective response (OR) defined as complete response (CR) or partial response (PR) out of the total number of participants randomized in each treatment group
Time Frame	Every 12 weeks up to 6 years

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Exemestane	Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily
Measure Participants	43	41
Number [percentage of participants]	23.3 54.2%	12.2 29.8%

3. Secondary Outcome

Title	Duration of Response (DR)
Description	Duration of objective response (complete response [CR] or partial response [PR]) calculated from date objective response was first documented to date of progressive disease. For subjects proceeding from PR to CR, the onset of PR was taken as the onset of objective response.
Time Frame	Every 12 weeks up to 6 years

Outcome Measure Data

Analysis Population Description

ITT.

Arm/Group Title	Exemestane	Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily
Measure Participants	43	41
Median (95% Confidence Interval) [months]	12.9	35.4

4. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	TTP = time between first day of study treatment and date of documented disease progression, or date of tumor-related death in the absence of previously documented progressive disease (PD). PD defined as a 25% or greater increase in size of 1 or more lesions compared to smallest previous assessment, or appearance of new lesion, or unequivocal worsening of bone lesions, or progression of nonevaluable lesions.
Time Frame	Every 12 weeks up to 6 years

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Exemestane	Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily
Measure Participants	43	41
Median (95% Confidence Interval) [months]	6.0	3.7

5. Secondary Outcome

Title	Time to Treatment Failure (TTF)
Description	TTF = time between first day of study treatment and date of diagnosis of progression, withdrawal from study treatment for any reason, administration of other antitumor treatment, or death from any cause, whichever was the earliest event.
Time Frame	Every 12 weeks up to 6 years

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Exemestane	Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily	Megestrol acetate 160 mg tablet taken once daily
Measure Participants	43	41
Median (95% Confidence Interval) [months]	6.0	3.7

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		Megestrol Acetate
Arm/Group Description	Exemestane 25 milligram (mg) oral tablet taken once daily		Megestrol acetate 160 mg tablet taken once daily
All Cause Mortality
	Exemestane		Megestrol Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exemestane		Megestrol Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		2/40 (5%)
General disorders
Chest pain NEC	0/41 (0%)		1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Back pain	0/41 (0%)		1/40 (2.5%)
Nervous system disorders
Cerebral haemorrhage	0/41 (0%)		1/40 (2.5%)
Headache NOS	0/41 (0%)		1/40 (2.5%)
Spinal cord compression	0/41 (0%)		1/40 (2.5%)
Psychiatric disorders
Completed suicide	1/41 (2.4%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Exemestane		Megestrol Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/41 (58.5%)		25/40 (62.5%)
Cardiac disorders
Supraventricular extrasystoles	1/41 (2.4%)		0/40 (0%)
Oedema NOS	0/41 (0%)		2/40 (5%)
Tachycardia NOS	0/41 (0%)		1/40 (2.5%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/41 (2.4%)		0/40 (0%)
Mouth ulceration	1/41 (2.4%)		0/40 (0%)
Nausea	6/41 (14.6%)		2/40 (5%)
Abdominal pain NOS	0/41 (0%)		1/40 (2.5%)
Abdominal pain upper	0/41 (0%)		1/40 (2.5%)
Constipation	0/41 (0%)		1/40 (2.5%)
General disorders
Chest pain NEC	1/41 (2.4%)		2/40 (5%)
Fatigue	1/41 (2.4%)		6/40 (15%)
Pain NOS	1/41 (2.4%)		0/40 (0%)
Thirst	1/41 (2.4%)		0/40 (0%)
Chest discomfort	0/41 (0%)		1/40 (2.5%)
Chest mass NOS	0/41 (0%)		1/40 (2.5%)
Oedema NOS	0/41 (0%)		1/40 (2.5%)
Infections and infestations
Influenza	3/41 (7.3%)		1/40 (2.5%)
Infection NOS	0/41 (0%)		2/40 (5%)
Injury, poisoning and procedural complications
Humerus fracture	0/41 (0%)		1/40 (2.5%)
Investigations
Aspartate aminotransferase	1/41 (2.4%)		1/40 (2.5%)
Weight increased	3/41 (7.3%)		5/40 (12.5%)
Alanine aminotransferase	0/41 (0%)		1/40 (2.5%)
Gamma-glutamyltransferase	0/41 (0%)		1/40 (2.5%)
Weight decreased	0/41 (0%)		1/40 (2.5%)
Metabolism and nutrition disorders
Hypercholesterolaemia	1/41 (2.4%)		2/40 (5%)
Hypertriglyceridaemia	2/41 (4.9%)		0/40 (0%)
Diabetes mellitus NOS	0/41 (0%)		1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/41 (4.9%)		0/40 (0%)
Back pain	2/41 (4.9%)		2/40 (5%)
Bone pain	2/41 (4.9%)		3/40 (7.5%)
Neck pain	1/41 (2.4%)		1/40 (2.5%)
Chest wall pain	0/41 (0%)		1/40 (2.5%)
Musculoskeletal pain	0/41 (0%)		1/40 (2.5%)
Nervous system disorders
Dizziness	1/41 (2.4%)		0/40 (0%)
Hypoaesthesia	1/41 (2.4%)		0/40 (0%)
Dizziness (exc vertigo)	0/41 (0%)		2/40 (5%)
Headache NOS	0/41 (0%)		1/40 (2.5%)
Insomnia NEC	0/41 (0%)		1/40 (2.5%)
Peripheral motor neuropathy	0/41 (0%)		1/40 (2.5%)
Spinal cord compression	0/41 (0%)		1/40 (2.5%)
Psychiatric disorders
Mood alteration NOS	0/41 (0%)		1/40 (2.5%)
Renal and urinary disorders
Dysuria	0/41 (0%)		1/40 (2.5%)
Haematuria	0/41 (0%)		1/40 (2.5%)
Urinary frequency	0/41 (0%)		1/40 (2.5%)
Reproductive system and breast disorders
Vaginal haemorrhage	2/41 (4.9%)		0/40 (0%)
Breast mass NOS	0/41 (0%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Cough	5/41 (12.2%)		4/40 (10%)
Dyspnoea NOS	3/41 (7.3%)		2/40 (5%)
Haemoptysis	0/41 (0%)		1/40 (2.5%)
Skin and subcutaneous tissue disorders
Face eodema	1/41 (2.4%)		0/40 (0%)
Nail discolouration	1/41 (2.4%)		0/40 (0%)
Pigmentation disorder	1/41 (2.4%)		0/40 (0%)
Sweating increased	5/41 (12.2%)		4/40 (10%)
Alopecia	0/41 (0%)		1/40 (2.5%)
Vascular disorders
Flushing	5/41 (12.2%)		0/40 (0%)

Limitations/Caveats

At the time of study completion in 2007, via protocol amendment participants still on treatment were allowed to continue treatment, being monitored for Serious Adverse Events (SAE) only. The final participant discontinued in 2009.

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.