Trial Outcomes & Findings for Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer (NCT NCT00375752)
NCT ID: NCT00375752
Last Updated: 2017-06-26
Results Overview
Sum of longest diameter for all target lesions was reported as baseline sum LD. Baseline sum LD was used as reference to characterize objective tumor response. Response Evaluation Criteria in Solid Tumors has 4 response categories. CR (complete response) = disappearance of all target lesions, PR (partial response)= 30% decrease in sum of longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD(stable disease)=small changes that do not meet criteria. Analysis was underpowered due to insufficient recruitment rate.
TERMINATED
PHASE4
168 participants
6 months
2017-06-26
Participant Flow
Participant milestones
| Measure |
Letrozole (LET)
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Overall Study
STARTED
|
79
|
89
|
|
Overall Study
COMPLETED
|
67
|
74
|
|
Overall Study
NOT COMPLETED
|
12
|
15
|
Reasons for withdrawal
| Measure |
Letrozole (LET)
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
4
|
4
|
|
Overall Study
Adverse Event
|
1
|
6
|
|
Overall Study
Withdrawal by Subject
|
6
|
1
|
|
Overall Study
Abnormal Laboratory Value(s)
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
2
|
|
Overall Study
Administrative Problems
|
0
|
1
|
Baseline Characteristics
Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
Baseline characteristics by cohort
| Measure |
Letrozole (LET)
n=79 Participants
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
n=89 Participants
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
Total
n=168 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.5 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
71.3 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
70.9 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
79 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
168 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: The modified intent-to-treat (mITT) population included all patients of the ITT population for whom at least one post-baseline assessment of tumor response according to modified RECIST made by central review was available.
Sum of longest diameter for all target lesions was reported as baseline sum LD. Baseline sum LD was used as reference to characterize objective tumor response. Response Evaluation Criteria in Solid Tumors has 4 response categories. CR (complete response) = disappearance of all target lesions, PR (partial response)= 30% decrease in sum of longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD(stable disease)=small changes that do not meet criteria. Analysis was underpowered due to insufficient recruitment rate.
Outcome measures
| Measure |
Letrozole (LET)
n=66 Participants
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
n=65 Participants
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Tumor Response Rate (Complete Response (CR) or Partial Response (PR)) Based on MRI- or Mammography and/or Sonography According to Modified RECIST Criteria at Month 6
|
54.5 percentage of participants
Interval 41.8 to 66.9
|
69.2 percentage of participants
Interval 56.6 to 80.1
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: The modified intent-to-treat (mITT) population included all patients of the ITT population for whom at least one post-baseline assessment of tumor response according to modified RECIST made by central review was available.
Best response is defined as the best response the patients has reached during the 6 months of treatment. Response Evaluation Criteria in Solid Tumors (RECIST) has 4 response categories. CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet criteria.
Outcome measures
| Measure |
Letrozole (LET)
n=66 Participants
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
n=65 Participants
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Best RECIST Response Based on Central Review at 6 Mos
Complete Response (CR)
|
0 Participants
|
2 Participants
|
|
Best RECIST Response Based on Central Review at 6 Mos
at least Paratial Response (PR)
|
36 Participants
|
43 Participants
|
|
Best RECIST Response Based on Central Review at 6 Mos
at least Stable Disease (SD)
|
30 Participants
|
19 Participants
|
|
Best RECIST Response Based on Central Review at 6 Mos
Progressive Disease
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Every 6 monthsPopulation: The intent-to-treat (ITT) population included all patients of the safety population for whom at least one post-baseline assessment of tumor response according to the modified RECIST (local or central assessment) was available. During different time points, participants with observations at that timepoint were included in the analysis.
Outcome measures
| Measure |
Letrozole (LET)
n=75 Participants
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
n=81 Participants
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Number of Patients With Breast Conserving Surgery at 6 Months
Surgery performed
|
66 Participants
|
77 Participants
|
|
Number of Patients With Breast Conserving Surgery at 6 Months
Radical mastectomy
|
10 Participants
|
12 Participants
|
|
Number of Patients With Breast Conserving Surgery at 6 Months
Modfied radical mastectomy
|
3 Participants
|
8 Participants
|
|
Number of Patients With Breast Conserving Surgery at 6 Months
Lumpectomy/Quadrantectomy
|
50 Participants
|
56 Participants
|
|
Number of Patients With Breast Conserving Surgery at 6 Months
Lumpectomy/Quadrantectomy + Other
|
1 Participants
|
1 Participants
|
|
Number of Patients With Breast Conserving Surgery at 6 Months
Other
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: The modified intent-to-treat (mITT) population included all patients of the ITT population for whom at least one post-baseline assessment of tumor response according to modified RECIST made by central review was available.
Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.
Outcome measures
| Measure |
Letrozole (LET)
n=66 Participants
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
n=65 Participants
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Change From Baseline in Tumor Size (Longest Diameter) at Month 6
|
-1.12 cm
Standard Deviation 0.92
|
-1.37 cm
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: baseline and 6 mosPopulation: ITT
The FACT-B total score is calculated by summing all five unweighted subscale scores, with total scores in the range of 0-144.To Derive a FACT-B total score: all sections added together The higher the score the better the QoL * \+ \_\_\_\_\_\_\_\_\_\_ + \_\_\_\_\_\_\_\_\_\_ + \_\_\_\_\_\_\_\_\_\_ + \_\_\_\_\_\_\_\_\_\_ =\_\_\_\_\_\_\_\_=FACT-B Total score (PWB score) (SWB score) (EWB score) (FWB score) (BCS score)
Outcome measures
| Measure |
Letrozole (LET)
n=67 Participants
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole +Zoledronic Acid (LET+ZOL)
n=68 Participants
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)
Baseline
|
113.3 score on a scale
Standard Deviation 16.6
|
109.5 score on a scale
Standard Deviation 20.2
|
|
Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)
Month 6
|
112.0 score on a scale
Standard Deviation 19.6
|
108.2 score on a scale
Standard Deviation 20.5
|
Adverse Events
Letrozole
Letrozole Plus Zoledronic Acid
Serious adverse events
| Measure |
Letrozole
n=79 participants at risk
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole Plus Zoledronic Acid
n=89 participants at risk
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.3%
1/79 • through study completion
|
0.00%
0/89 • through study completion
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Gastrointestinal disorders
Gastric ulcer perforation
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
General disorders
General physical health deterioration
|
0.00%
0/79 • through study completion
|
3.4%
3/89 • through study completion
|
|
General disorders
Performance status decreased
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
General disorders
Swelling
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Infections and infestations
Appendicitis perforated
|
1.3%
1/79 • through study completion
|
0.00%
0/89 • through study completion
|
|
Infections and infestations
Bronchitis
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Infections and infestations
Wound infection
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Accident
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/79 • through study completion
|
4.5%
4/89 • through study completion
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Injury, poisoning and procedural complications
Seroma
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Investigations
Blood sodium decreased
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.3%
1/79 • through study completion
|
0.00%
0/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
1.3%
1/79 • through study completion
|
0.00%
0/89 • through study completion
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Nervous system disorders
Amnesia
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Nervous system disorders
Dementia
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Nervous system disorders
Dizziness
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Vascular disorders
Arterial insufficiency
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Vascular disorders
Haematoma
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Vascular disorders
Venous thrombosis
|
0.00%
0/79 • through study completion
|
1.1%
1/89 • through study completion
|
Other adverse events
| Measure |
Letrozole
n=79 participants at risk
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
|
Letrozole Plus Zoledronic Acid
n=89 participants at risk
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
5.1%
4/79 • through study completion
|
4.5%
4/89 • through study completion
|
|
Gastrointestinal disorders
Constipation
|
7.6%
6/79 • through study completion
|
3.4%
3/89 • through study completion
|
|
Gastrointestinal disorders
Diarrhoea
|
8.9%
7/79 • through study completion
|
11.2%
10/89 • through study completion
|
|
Gastrointestinal disorders
Dry mouth
|
6.3%
5/79 • through study completion
|
0.00%
0/89 • through study completion
|
|
Gastrointestinal disorders
Nausea
|
10.1%
8/79 • through study completion
|
13.5%
12/89 • through study completion
|
|
General disorders
Chills
|
0.00%
0/79 • through study completion
|
5.6%
5/89 • through study completion
|
|
General disorders
Fatigue
|
16.5%
13/79 • through study completion
|
22.5%
20/89 • through study completion
|
|
General disorders
Pyrexia
|
1.3%
1/79 • through study completion
|
5.6%
5/89 • through study completion
|
|
Infections and infestations
Nasopharyngitis
|
8.9%
7/79 • through study completion
|
4.5%
4/89 • through study completion
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.8%
3/79 • through study completion
|
5.6%
5/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.3%
16/79 • through study completion
|
20.2%
18/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
3/79 • through study completion
|
5.6%
5/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
8.9%
7/79 • through study completion
|
21.3%
19/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/79 • through study completion
|
5.6%
5/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.3%
5/79 • through study completion
|
4.5%
4/89 • through study completion
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.5%
2/79 • through study completion
|
5.6%
5/89 • through study completion
|
|
Nervous system disorders
Headache
|
10.1%
8/79 • through study completion
|
9.0%
8/89 • through study completion
|
|
Psychiatric disorders
Depression
|
3.8%
3/79 • through study completion
|
6.7%
6/89 • through study completion
|
|
Psychiatric disorders
Insomnia
|
3.8%
3/79 • through study completion
|
6.7%
6/89 • through study completion
|
|
Psychiatric disorders
Sleep disorder
|
6.3%
5/79 • through study completion
|
1.1%
1/89 • through study completion
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.8%
3/79 • through study completion
|
10.1%
9/89 • through study completion
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.1%
4/79 • through study completion
|
3.4%
3/89 • through study completion
|
|
Vascular disorders
Hot flush
|
31.6%
25/79 • through study completion
|
21.3%
19/89 • through study completion
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until publication of the pooled data (i.e.,data from all sites)in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER