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Randomized Trial Of Exemestane Versus Continued Tamoxifen In Postmenopausal Women With Early Breast Cancer (IES)

This study has been completed.
Sponsor:
Collaborator:
International Collaborative Cancer Group (ICCG)
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00038467
First received: May 31, 2002
Last updated: April 21, 2014
Last verified: April 2014
Results First Received: March 5, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Breast Neoplasms
Interventions: Drug: Tamoxifen
Drug: Exemestane

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The publication describing study results (Coombes RC et al; N Engl J Med 350; 1119) stated that 4742 participants were enrolled in study. It was later discovered that 2 participants were randomized twice. Hence, 4740 participants were enrolled in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Main study also included 3 sub-studies only for the purpose of tolerability assessment: endometrial status, bone metabolism and quality of life (QoL). Out of 4740 enrolled participants, data for 16 participants from a center were excluded since it was considered unreliable. Results are reported for remaining 4724 participants.

Reporting Groups
  Description
Exemestane Participants diagnosed with breast cancer who remained disease-free after previously receiving 2 to 3 years of tamoxifen 20 milligram (mg) or 30 mg tablet-in-capsule orally once daily as per standard medical practice, received exemestane (Aromasin) 25 mg tablet-in-capsule orally once daily for the remainder of 5-year period.
Tamoxifen Participants diagnosed with breast cancer who remained disease-free after previously receiving 2 to 3 years of tamoxifen 20 mg or 30 mg tablet-in-capsule orally once daily as per standard medical practice, received the same dose of tamoxifen tablet-in-capsule orally once daily for the remainder of 5-year period.

Participant Flow:   Overall Study
    Exemestane     Tamoxifen  
STARTED     2352     2372  
Treated     2321 [1]   2337 [2]
COMPLETED     1810     1830  
NOT COMPLETED     542     542  
Adverse Event                 170                 145  
Withdrawal by Subject                 150                 107  
Protocol Violation                 19                 22  
Death                 22                 16  
Lost to Follow-up                 15                 10  
Recurrence                 109                 179  
Randomized, but not treated                 31                 35  
Unspecified                 26                 28  
[1] 8 participants randomized to receive exemestane, received tamoxifen. Reported as per randomization.
[2] 7 participants randomized to receive tamoxifen, received exemestane. Reported as per randomization.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population included all participants assigned to the treatment group to which they were randomized, irrespective of the treatment they actually received.

Reporting Groups
  Description
Exemestane Participants diagnosed with breast cancer who remained disease-free after previously receiving 2 to 3 years of tamoxifen 20 milligram (mg) or 30 mg tablet-in-capsule orally once daily as per standard medical practice, received exemestane (Aromasin) 25 mg tablet-in-capsule orally once daily for the remainder of 5-year period.
Tamoxifen Participants diagnosed with breast cancer who remained disease-free after previously receiving 2 to 3 years of tamoxifen 20 mg or 30 mg tablet-in-capsule orally once daily as per standard medical practice, received the same dose of tamoxifen tablet-in-capsule orally once daily for the remainder of 5-year period.
Total Total of all reporting groups

Baseline Measures
    Exemestane     Tamoxifen     Total  
Number of Participants  
[units: participants]
  2352     2372     4724  
Age  
[units: years]
Mean ± Standard Deviation
  63.78  ± 8.12     63.69  ± 8.22     63.73  ± 8.17  
Gender  
[units: participants]
     
Female     2352     2372     4724  
Male     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Disease-Free Survival (DFS) at Month 36 Post-Randomization: Main Study   [ Time Frame: Baseline up to Month 36 ]

2.  Secondary:   Overall Survival (OS) at Month 36 Post-Randomization: Main Study   [ Time Frame: Baseline up to Month 120 ]

3.  Secondary:   Number of Events of Second Breast Cancer in Contralateral Breast: Main Study   [ Time Frame: Baseline up to Month 120 ]

4.  Secondary:   Percent Change From Baseline in Lumbar Spine and Proximal Femur (Total Hip) Bone Mineral Density (BMD) at 6, 12, 24 Months On-treatment and 24 Months Post-treatment: Bone Metabolism Sub-study   [ Time Frame: Baseline, 6, 12, 24 months after randomization (on-treatment), 24 months post-treatment ]

5.  Secondary:   Percent Change From Baseline in Femoral Neck and Femoral Wards Bone Mineral Density (BMD) at 6, 12 and 24 Months On-treatment and 24 Months Post-treatment: Bone Metabolism Sub-study   [ Time Frame: Baseline, 6, 12, 24 months after randomization (on-treatment), 24 months post-treatment ]

6.  Secondary:   Change From Baseline in Lumbar Spine and Proximal Femur (Total Hip) Bone Mineral Density (BMD) T-scores at 6, 12 and 24 Months On-treatment and 24 Months Post-treatment: Bone Metabolism Sub-study   [ Time Frame: Baseline, 6, 12, 24 months after randomization (on-treatment), 24 months post-treatment ]

7.  Secondary:   Percentage of Bone Specific Alkaline Phosphatase (BAP) Serum Concentration Relative to Baseline: Bone Metabolism Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30 months after randomization (on-treatment), 36 months after randomization (end of treatment), 12, 24 months post-treatment ]

8.  Secondary:   Percentage of C-Terminal Telopeptide (CTX) Serum Concentration Relative to Baseline: Bone Metabolism Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30 months after randomization (on-treatment), 36 months after randomization (end of treatment), 12, 24 months post-treatment ]

9.  Secondary:   Percentage of Osteocalcin (OC) and Procollagen T1 C-Peptide (PICP) Serum Concentration Relative to Baseline: Bone Metabolism Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30 months after randomization (on-treatment), 36 months after randomization (end of treatment), 12, 24 months post-treatment ]

10.  Secondary:   Percentage of Deoxy-pyridinoline (DPD) Urine Concentration Relative to Baseline: Bone Metabolism Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30 months after randomization (on-treatment), 36 months after randomization (end of treatment), 12, 24 months post-treatment ]

11.  Secondary:   Percentage of N-telopeptide of Type 1 Collagen (NTX) Urine Concentration Relative to Baseline: Bone Metabolism Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30 months after randomization (on-treatment), 36 months after randomization (end of treatment), 12, 24 months post-treatment ]

12.  Secondary:   Number of Participants With Fracture: Bone Metabolism Sub-study   [ Time Frame: Baseline up to 24 months post-treatment ]

13.  Secondary:   Change From Baseline in Treatment Outcome Index (TOI) at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

14.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy – Endocrine Subscale (FACT-ES) Total Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

15.  Secondary:   Change From Baseline in Total Functional Assessment of Cancer Therapy – General Breast and Endocrine (FACT-GBE) Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

16.  Secondary:   Change From Baseline in Physical Well-Being (PWB) Subscale Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

17.  Secondary:   Change From Baseline in Social/Family Well-Being (SWB) Sub-scale Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

18.  Secondary:   Change From Baseline in Relationship With Doctor (RWD) Subscale Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Substudy   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

19.  Secondary:   Change From Baseline in Emotional Well-Being (EWB) Subscale Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

20.  Secondary:   Change From Baseline in Functional Well-Being (FWB) Sub-scale Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

21.  Secondary:   Change From Baseline in Breast Cancer Subscale (BCS) Score at 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 Months: QoL Sub-study   [ Time Frame: Baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48, 60 months after randomization ]

22.  Secondary:   Number of Participants With Severe Endocrine Symptoms: QoL Sub-study   [ Time Frame: Baseline up to 24 months after randomization ]

23.  Secondary:   Percentage of Participants With Endometrial Thickness Greater Than or Equal to (>=) 5 Millimeter (mm): Endometrial Sub-study   [ Time Frame: 6, 12, 24, 36 months after randomization, 6, 12, 24 months post-treatment ]

24.  Secondary:   Endometrial Thickness: Endometrial Sub-study   [ Time Frame: Baseline, 6, 12, 24, 36 months after randomization, 6, 12, 24 months post-treatment ]

25.  Secondary:   Uterine and Overall Ovary Volume: Endometrial Sub-study   [ Time Frame: 6, 12, 24, 36 months after randomization, 6, 12, 24 months post-treatment ]

26.  Secondary:   Number of Participants With Polyps, Fibroids and Ovarian Cysts: Endometrial Sub-study   [ Time Frame: 6, 12, 24, 36 months after randomization, 6, 12, 24 months post-treatment ]

27.  Secondary:   Percentage of Participants With at Least 1 Gynecological Symptoms: Endometrial Sub-study   [ Time Frame: Baseline up to 24 months post-treatment ]

28.  Secondary:   Number of Participants With Histological Findings: Endometrial Sub-study   [ Time Frame: Baseline up to 24 months post-treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Other AEs included both SAEs and AEs. Non-SAE could not be presented separately for this study as AEs were collected in clinical database where SAE flags were not collected.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided


Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00038467     History of Changes
Other Study ID Numbers: 96-OEXE-031, A5991012
Study First Received: May 31, 2002
Results First Received: March 5, 2014
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration