A Phase 3 interventional study of letrozole and placebo in Breast Cancer, sponsored by Canadian Cancer Trials Group. Completed at 43 sites in 2 countries. Open to female participants aged 0 Years to 120 Years. Per ClinicalTrials.gov, last updated 2023-08-25.
Sponsored by Canadian Cancer Trials Group · Phase 3, Interventional, and Treatment
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating in women with breast cancer who have already received 5 years of aromatase inhibitor therapy.
PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating women with primary breast cancer who have received 5 years of aromatase inhibitor therapy.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and study randomization (\< 6 months vs 6 months to 2 years), and duration of prior tamoxifen citrate use (0 vs \< 2 years vs 2 - 4½ years vs > 4½ years). Patients are randomized to 1 of 2 treatment arms.
Patients undergo bone mineral density measurement by DEXA scan at baseline (if not done within 12 months of study entry), at 24 and 48 months during study therapy, and at the completion of study therapy. Some patients also complete quality-of-life questionnaires at baseline and at 12, 24, 36, 48, and 60 months.
After completion of study therapy, patients are followed annually.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 1,918 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Canadian Cancer Trials Group is the lead sponsor of 91 studies on the registry; 28 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.
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DISEASE CHARACTERISTICS:
Must have received 4½ - 6 years of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane), either as initial therapy or after prior tamoxifen citrate, including treatment received as part of clinical trial CAN-NCIC-MA17
No metastatic or recurrent disease, contralateral breast cancer, or ductal carcinoma in situ in either breast, as determined by the following:
Hormone-receptor status:
PATIENT CHARACTERISTICS:
Able (i.e. sufficiently fluent) and willing to complete quality-of-life questionnaires in either English or French (NCIC CTG participating centers)
PRIOR CONCURRENT THERAPY:
Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.
Drug: letrozole
Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.
Other: placebo
Given orally
Also known as: femara
Given orally
Also known as: sugar pill
Disease-free Survival (DFS)
It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.
Time frame: Unitil the end of study with a median follow up of 75 months
Incidence of Contralateral Breast Cancer
The annual incidence rate was estimated based on the time to the development of contralateral breast cancer, which was calculated in months from the day of randomization to the diagnosis date of contralateral breast cancer for subjects who had developed the contralateral breast cancer, to the time of death for the patient who died, or to the last day the patient was known alive for subjects without contralateral breast cancer
Time frame: 10 years
Overall Survival (OS)
For subjects who died, overall survival was calculated in months from the day of randomization to the date of death. Otherwise, survival was censored at the last day the patient was known to be alive. Probability of overall survival at 5 years is estimated and reported.
Time frame: Until the end of study with a median follow-up of 75 months
Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey
Difference between post baseline scores and baseline score of role function-physical scale on SF-36 Health Survey (scale range between 0 and 100 with higher score indicating better quality of life).
Time frame: 8 years
| Milestone | Letrozole | Placebo |
|---|---|---|
| Started | 959 | 959 |
| Completed | 959 | 959 |
| Not completed | 0 | 0 |
It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.
| probability of DFS at 5 years | Letrozole | Placebo |
|---|---|---|
| Disease-free Survival (DFS) | 0.95 (0.93 to 0.96) | 0.91 (0.89 to 0.93) |
The annual incidence rate was estimated based on the time to the development of contralateral breast cancer, which was calculated in months from the day of randomization to the diagnosis date of contralateral breast cancer for subjects who had developed the contralateral breast cancer, to the time of death for the patient who died, or to the last day the patient was known alive for subjects without contralateral breast cancer
| Number of new case per 1000 person years | Letrozole | Placebo |
|---|---|---|
| Incidence of Contralateral Breast Cancer | 2.1 (1.0 to 3.2) | 4.9 (3.2 to 6.7) |
For subjects who died, overall survival was calculated in months from the day of randomization to the date of death. Otherwise, survival was censored at the last day the patient was known to be alive. Probability of overall survival at 5 years is estimated and reported.
| probability of OS at 5 years | Arm I | Arm II |
|---|---|---|
| Overall Survival (OS) | 0.93 (0.92 to 0.95) | 0.94 (0.92 to 0.95) |
Difference between post baseline scores and baseline score of role function-physical scale on SF-36 Health Survey (scale range between 0 and 100 with higher score indicating better quality of life).
| score on a scale | Letrozole | Placebo |
|---|---|---|
| Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey | -7.74 ± 1.09 | -6.28 ± 1.08 |
Collected over During protocol treatment of 5 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I | 100/959 (10.4%) | 15/959 (1.6%) | 863/959 (90%) |
| Arm II | 100/954 (10.5%) | 19/954 (2%) | 841/954 (88.2%) |
| Event | Arm I | Arm II |
|---|---|---|
| Cardiac-ischemia/infarctionCardiac disorders | 2/959 | 4/954 |
| Sudden deathGeneral disorders | 4/959 | 1/954 |
| Infection without neutropeniaInfections and infestations | 2/959 | 3/954 |
| CNS cerebrovascular ischemiaNervous system disorders | 0/959 | 3/954 |
| Second malignacyNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/959 | 3/954 |
| Renal failureRenal and urinary disorders | 3/959 | 2/954 |
| Pulmonary - OtherRespiratory, thoracic and mediastinal disorders | 0/959 | 2/954 |
| Cardiac troponin I (cTnI)Cardiac disorders | 0/959 | 1/954 |
| Thrombosis/embolismCardiac disorders | 0/959 | 1/954 |
| Constitutional Symptoms - OtherGeneral disorders | 0/959 | 1/954 |
| Event | Arm I | Arm II |
|---|---|---|
| ArthralgiaGeneral disorders | 513/959 | 475/954 |
| Hot flashes/ flushesEndocrine disorders | 360/959 | 354/954 |
| FatigueGeneral disorders | 346/959 | 355/954 |
| ArthritisMusculoskeletal and connective tissue disorders | 317/959 | 288/954 |
| InsomniaNervous system disorders | 269/959 | 243/954 |
| MyalgiaGeneral disorders | 268/959 | 240/954 |
| HypercholesterolemiaMetabolism and nutrition disorders | 203/959 | 184/954 |
| SweatingGeneral disorders | 176/959 | 175/954 |
| Bone painGeneral disorders | 174/959 | 133/954 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 148/959 | 165/954 |
| Age, Continuous(years) | Letrozole | Placebo | Total |
|---|---|---|---|
| Median | 65.6 (43 to 92.2) | 64.8 (43.4 to 89.9) | 65.1 (43 to 92.2) |
| Sex: Female, Male(Participants) | Letrozole | Placebo | Total |
|---|---|---|---|
| Female | 959 | 959 | 1918 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Letrozole | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 11 | 13 | 24 |
| Not Hispanic or Latino | 940 | 939 | 1879 |
| Unknown or Not Reported | 8 | 7 | 15 |
| Region of Enrollment(Participants) | Letrozole | Placebo | Total |
|---|---|---|---|
| Canada | 276 | 285 | 561 |
| United States | 683 | 674 | 1357 |
| ECOG Performance Status(Participants) | Letrozole | Placebo | Total |
|---|---|---|---|
| Grade 0 | 852 | 856 | 1708 |
| Grade 1 | 100 | 95 | 195 |
| Grade 2 | 7 | 8 | 15 |
Plan to share: No
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Canadian Cancer Trials Group