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| ID | Type | Description | Link |
|---|---|---|---|
| IBCSG-35-07-SUBSTUDY | Other Identifier | IBCSG | |
| BIG-1-07-SUBSTUDY | Other Identifier | Breast International Group | |
| 2007-001370-88 | EudraCT Number | ||
| EU-21101 |
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RATIONALE: Studying samples of blood in the laboratory from patients receiving treatment for cancer may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.
PURPOSE: This clinical trial is studying changes in estrogen levels and grip strength in postmenopausal women who have received 4 to 6 years of hormone therapy for breast cancer and are currently receiving letrozole on clinical trial IBCSG-35-07.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
All patients undergo blood sample collection at baseline for the analysis of single nucleotide polymorphisms, after randomization on clinical trial IBCSG-35-07 and prior to the beginning treatment on IBCSG-35-07. Patients also undergo serum collection at baseline and at 9, 10.5, and 12 months for the analysis of estrogen levels and sex hormone binding globulins. Patients undergo measurement of grip strength at baseline and at 9 and 12 months. Samples may be banked for future research studies.
Patients complete quality-of-life questionnaires (Breast Cancer Prevention Trial [BCPT] Symptom Scales on Form 35-PRS and IBCSG Trial 35-07 QL Form) periodically.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| polymorphism analysis | Genetic | SNPs will be genotyped in whole blood samples taken at baseline. | ||
| laboratory biomarker analysis | Other | Biomarkers will be assessed in blood and serum samples at different time points. | ||
| quality-of-life assessment | Procedure | Quality of life will be assessed using the Breast Cancer Prevention Trial (BCPT) Symptom Scales and the IBCSG Trial 35-07 QL Form. |
| Measure | Description | Time Frame |
|---|---|---|
| Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population | In SOLE-EST, levels of E1, E2, and E1S were summarized over time at 0 (baseline), 9, 10.5, and 12 months from randomization among patients in the longitudinal analysis population (N=90 with post-baseline sample). | 0 (baseline), 9, 10.5, and 12 months from randomization |
| Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group | Changes in hormone levels (E1, E2, and E1S levels), as percentage change over time according to treatment assignment (at 9, 10.5 and 12 months from baseline). | 9, 10.5, and 12 months from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia | Toxicity grade changes from 6 to 12 months (hot flashes, insomnia and arthralgia; Common Terminology Criteria for Adverse Events (CTCAE) version 3 values 1- 4 grouped as no change, increase in grade [worsening] or decrease in grade [improvement]) | 6 and 12 months |
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DISEASE CHARACTERISTICS:
Previously diagnosed with breast cancer
Disease-free following 4-6 years of prior adjuvant endocrine therapy with selective estrogen-receptor modulators and/or aromatase inhibitors
Patient must be currently enrolled on clinical trial IBCSG-35-07 as well as the Quality-of-Life substudy
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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Patients randomized to the SOLE trial (IBCSG 35-07) and participate in the Quality of Life substudy.
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| Name | Affiliation | Role |
|---|---|---|
| Jacquie Chirgwin, MD | Box Hill Hospital | Study Chair |
| Guy Jerusalem, MD, PhD | CHU Liege - Domaine Universitaire du Sart Tilman | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Box Hill Hospital | Box Hill | Victoria | 3128 | Australia | ||
| CHU Liege - Domaine Universitaire du Sart Tilman |
There were 104 patients enrolled during the active period (25 continuous letrozole, 79 intermittent letrozole). Blood samples were obtained from 103 patients at baseline. For the longitudinal analysis, patients (N=90) were included if they had at least one post-baseline sample. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent) and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in longitudinal analyses.
The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST). SOLE was a multinational study performed in 240 centers of the Breast International Group-affiliated cooperative groups in 22 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Continuous Letrozole Treatment Group | The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST).Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Baseline Population |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 6, 2007 |
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Serum, whole blood,
| Quality of Life (QoL) Score Changes |
All patients in SOLE-EST were assessed for symptom specific QoL. QoL changes from 6 to 12 months (sleep change, hot flushes, tiredness, difficulties of becoming aroused, loss of sexual interest, physical wellbeing and mood; LASA (linear analogue self-assessment) scores 0-100 (higher is better QoL) were calculated as 12 months minus 6 months, so that negative is worsening and positive is improvement. |
| 6 and 12 months: Change is calculated from 12 months minus 6 months, therefore positive values indicate an improved condition and negative values indicate a declined condition |
| Change in Grip-strength Score in the Dominant Hand | Grip strength was measured using the Martin Vigorimeter (a modified sphygmomanometer which measures the force of compression in kilo pascal by means of a compressible rubber ball). To perform the hand grip test, the patients were asked to squeeze the ball of a modified sphygmomanometer three times with maximal force and the maximal value of three trials of each hand were used for evaluation. Higher value represents greater strength, thus changes are calculated as 12 months minus 9 months so that positive is improved condition and negative is declined condition. | Changes in grip strength score is calculated at 12 months minus 9 months |
| Liège |
| B-4000 |
| Belgium |
| FG001 | Intermittent Letrozole Treatment Group | The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST).Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5). |
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| NOT COMPLETED |
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| Analysis Population (Baseline) |
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| Analysis Population (9 Months) |
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| Analysis Population (10.5 Months) |
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| Analysis Population (12 Months) |
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Postmenopausal woman with hormone receptor-positive, lymph node-positive, and operable breast cancer of any age were included in the study. They must have undergone local treatment and have completed 4-6 years of adjuvant endocrine therapy. At enrollment, they had to be clinically free of breast cancer without any evidence of recurrence. Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST.
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| ID | Title | Description |
|---|---|---|
| BG000 | Continuous Letrozole Treatment Group | Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5). |
| BG001 | Intermittent Letrozole Treatment Group | Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Body Mass Index (BMI) at randomization | Count of Participants | Participants |
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| Type of menopause | Count of Participants | Participants |
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| Last (most recent) type of prior endocrine therapy (ET) | Count of Participants | Participants |
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| Duration of prior AI | Count of Participants | Participants |
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| Duration from end of prior ET to randomization | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population | In SOLE-EST, levels of E1, E2, and E1S were summarized over time at 0 (baseline), 9, 10.5, and 12 months from randomization among patients in the longitudinal analysis population (N=90 with post-baseline sample). | Longitudinal analysis group: There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85, 84, and 81, respectively, could be included in analyses of hormone levels over time. | Posted | Median | Inter-Quartile Range | pg/mL | 0 (baseline), 9, 10.5, and 12 months from randomization |
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| Primary | Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group | Changes in hormone levels (E1, E2, and E1S levels), as percentage change over time according to treatment assignment (at 9, 10.5 and 12 months from baseline). | Longitudinal Analysis Population: There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. 90 patients at baseline, 85 patients at month 9, 84 patients at month 10.5, and 81 patients at month 12. | Posted | Median | Inter-Quartile Range | percentage change | 9, 10.5, and 12 months from baseline |
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| Secondary | Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia | Toxicity grade changes from 6 to 12 months (hot flashes, insomnia and arthralgia; Common Terminology Criteria for Adverse Events (CTCAE) version 3 values 1- 4 grouped as no change, increase in grade [worsening] or decrease in grade [improvement]) | In total, 76/85 patients (19 continuous; 57 intermittent) who had a 9 month sample also had a sample at 12 months and are included in analyses relating E2 change (9 to 12m) with QL, grip strength and adverse event (AE) changes. | Posted | Median | Inter-Quartile Range | toxicity grade | 6 and 12 months |
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| Secondary | Quality of Life (QoL) Score Changes | All patients in SOLE-EST were assessed for symptom specific QoL. QoL changes from 6 to 12 months (sleep change, hot flushes, tiredness, difficulties of becoming aroused, loss of sexual interest, physical wellbeing and mood; LASA (linear analogue self-assessment) scores 0-100 (higher is better QoL) were calculated as 12 months minus 6 months, so that negative is worsening and positive is improvement. | In total, 76/85 patients (19 continuous; 57 intermittent) who had a 6 month sample also had a sample at 12 months and are included in analyses relating E2 change (6 to 12m) with QL, grip strength and AE changes. | Posted | Median | Inter-Quartile Range | score on a scale | 6 and 12 months: Change is calculated from 12 months minus 6 months, therefore positive values indicate an improved condition and negative values indicate a declined condition |
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| Secondary | Change in Grip-strength Score in the Dominant Hand | Grip strength was measured using the Martin Vigorimeter (a modified sphygmomanometer which measures the force of compression in kilo pascal by means of a compressible rubber ball). To perform the hand grip test, the patients were asked to squeeze the ball of a modified sphygmomanometer three times with maximal force and the maximal value of three trials of each hand were used for evaluation. Higher value represents greater strength, thus changes are calculated as 12 months minus 9 months so that positive is improved condition and negative is declined condition. | Longitudinal analysis population N=90 (21 Continuous letrozole; 69 Intermittent letrozole); N samples per timepoint: N=90 at baseline, N=85 at month 9; N= 84 at month 10.5, N=81 at month 12. In total, 76/85 patients (19 continuous; 57 intermittent) who had a 9 month sample also had a sample at 12 months and are included in analyses relating E2 change (9 to 12m) with grip strength. | Posted | Median | Inter-Quartile Range | kilopascals | Changes in grip strength score is calculated at 12 months minus 9 months |
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Adverse event (AE) information were collected at baseline and at 6 and 12 months in the SOLE main study.
Adverse event (AE) information were collected at baseline and at 6 and 12 months in the SOLE main study, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0). Primary AEs for the SOLE-EST substudy are arthralgia, hot flushes and insomnia (reported in the results module).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Continuous Letrozole Treatment Group | Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5). | 0 | 25 | 0 | 25 | 0 | 25 |
| EG001 | Intermittent Letrozole Treatment Group | Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5). | 0 | 78 | 0 | 78 | 0 | 78 |
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After 5 years of adjuvant endocrine therapy, resistant tumoral cells could be different from those present at initial diagnosis, and the apoptotic effect of estrogen on these cells might be insufficient. It is possible that the intermittent treatment was given too late.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head Trial Activities and Deputy Director: Dr. Heidi Roschitzki-Voser | International Breast Cancer Study Group (IBCSG) | +41 31 511 94 00 | heidi.roschitzki@ibcsg.org |
| Mar 24, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D054458 | Amplified Fragment Length Polymorphism Analysis |
| ID | Term |
|---|---|
| D016172 | DNA Fingerprinting |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
| D016133 | Polymerase Chain Reaction |
| D021141 | Nucleic Acid Amplification Techniques |
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| 55-59 |
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| 60-64 |
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| 65-69 |
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| ≥70 |
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| OG002 | Continuous Letrozole Treatment Arm (10.5 Months) | There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time. |
| OG003 | Intermittent Letrozole Treatment Group (10.5 Months) | There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time. |
| OG004 | Continuous Letrozole Treatment Arm (12 Months) | There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time. |
| OG005 | Intermittent Letrozole Treatment Group (12 Months) | There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time. |
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| Units | Counts |
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| Participants |
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| Intermittent Letrozole Treatment Group |
Longitudinal analysis population N=90 (21 Continuous letrozole; 69 Intermittent letrozole); N samples per timepoint: N=90 at baseline, N=85 at month 9; N= 84 at month 10.5, N=81 at month 12. In total, 76/85 patients (19 continuous; 57 intermittent) who had a 9 month sample also had a sample at 12 months and are included in analyses relating E2 change (9 to 12m) with QL, grip strength and AE changes. |
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