Trial Outcomes & Findings for Clodronate With or Without Chemotherapy and/or Hormonal Therapy in Treating Women With Stage I or Stage II Breast Cancer (NCT NCT00009945)

NCT ID: NCT00009945

Last Updated: 2017-12-13

Results Overview

Time to first event where an event is any recurrences, 2nd primary or death to determine the percentage of patients disease free at 8 years

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 3323 participants
• Primary outcome timeframe: 8 years
• Results posted on: 2017-12-13

Participant Flow

Participant milestones

Measure	Arm 1: Clodronate Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Overall Study STARTED	1662	1661
Overall Study COMPLETED	1655	1656
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Measure	Arm 1: Clodronate Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Overall Study no follow up data	7	5

Baseline Characteristics

Clodronate With or Without Chemotherapy and/or Hormonal Therapy in Treating Women With Stage I or Stage II Breast Cancer

Baseline characteristics by cohort

Measure	Clodronate n=1662 Participants Clodronate	Placebo n=1661 Participants Placebo	Total n=3323 Participants Total of all reporting groups
Age, Continuous	54 years STANDARD_DEVIATION 10.5 • n=5 Participants	53 years STANDARD_DEVIATION 10.4 • n=7 Participants	54 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	1662 Participants n=5 Participants	1661 Participants n=7 Participants	3323 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: 8 years

Time to first event where an event is any recurrences, 2nd primary or death to determine the percentage of patients disease free at 8 years

Outcome measures

Measure	Arm 1: Clodronate n=1655 Participants Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo n=1656 Participants Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Disease Free Survival.	81.0 percentage of patients	79.6 percentage of patients

SECONDARY outcome

Timeframe: 8 years

Time from randomization to first diagnosis of skeletal metastasis to determine the percentage of patient free of skeletal metastasis at 8 years

Outcome measures

Measure	Arm 1: Clodronate n=1655 Participants Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo n=1656 Participants Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Skeletal Metastasis Free Survival	95.7 percentage of patients	94.6 percentage of patients

SECONDARY outcome

Timeframe: 8 years

Time from randomization to any death to determine the percentage of patients alive at 8 years

Outcome measures

Measure	Arm 1: Clodronate n=1655 Participants Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo n=1656 Participants Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Overall Survival	90.6 percentage of patients	89.3 percentage of patients

SECONDARY outcome

Timeframe: 8 years

Time from randomization to any local, regional, or distant recurrence of breast cancer to determine the percentage of patients relapse free at 8 years

Outcome measures

Measure	Arm 1: Clodronate n=1655 Participants Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo n=1656 Participants Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Relapse Free Survival	89.9 percentage of patients	88.3 percentage of patients

SECONDARY outcome

Timeframe: 8 years

Time from randomization to incidence of non-skeletal metastasis to determine the percentage of patients free from non-skeletal metastasis at 8 years

Outcome measures

Measure	Arm 1: Clodronate n=1655 Participants Patient receives 2 tablets once daily for 3 years. clodronate: 1600 mg PO daily	Arm 2: Placebo n=1656 Participants Patient receives 2 tablets once daily for 3 years. placebo: 2 pills PO daily
Incidence of Non-skeletal Metastasis	94.8 percentage of patients	93.2 percentage of patients

Adverse Events

Clodronate

Serious events: 340 serious events

Other events: 73 other events

Deaths: 5 deaths

Placebo

Serious events: 350 serious events

Other events: 107 other events

Deaths: 12 deaths

Serious adverse events

Measure	Clodronate n=1612 participants at risk Clodronate	Placebo n=1623 participants at risk Placebo
Gastrointestinal disorders Abdominal pain	0.50% 8/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Acidosis	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Activated partial thromboplastin time prolonged	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Alanine aminotransferase increased (ALT/SGPT)	0.93% 15/1612 Participants at Risk includes any patient who submitted an AE form.	0.43% 7/1623 Participants at Risk includes any patient who submitted an AE form.
Skin and subcutaneous tissue disorders Alopecia	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Anal fistula	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.12% 2/1623 Participants at Risk includes any patient who submitted an AE form.
Blood and lymphatic system disorders Anemia	0.62% 10/1612 Participants at Risk includes any patient who submitted an AE form.	0.49% 8/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Anorexia	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Psychiatric disorders Anxiety	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Apnea	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Arthralgia	0.56% 9/1612 Participants at Risk includes any patient who submitted an AE form.	0.49% 8/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Arthritis	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Aspartate aminotransferase increased (AST/SGOT)	0.62% 10/1612 Participants at Risk includes any patient who submitted an AE form.	0.43% 7/1623 Participants at Risk includes any patient who submitted an AE form.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Bone pain	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.49% 8/1623 Participants at Risk includes any patient who submitted an AE form.
Injury, poisoning and procedural complications Bruising	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Cardiac disorders - Other, specify	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.12% 2/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Cardiac troponin I increased	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Cardiac troponin T increased	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Eye disorders Cataract	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.37% 6/1623 Participants at Risk includes any patient who submitted an AE form.
Infections and infestations Catheter related infection	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Cholesterol high	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Cognitive disturbance	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Colitis	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Conduction disorder	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Psychiatric disorders Confusion	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Constipation	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations CPK increased	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Creatinine increased	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Dehydration	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
Psychiatric disorders Depression	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.62% 10/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Diarrhea	1.8% 29/1612 Participants at Risk includes any patient who submitted an AE form.	0.62% 10/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Dizziness	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Dry mouth	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Dysgeusia	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Dyspepsia	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Dysphasia	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.56% 9/1612 Participants at Risk includes any patient who submitted an AE form.	0.80% 13/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Esophagitis	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Extrapyramidal disorder	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Eye disorders Eye disorders - Other, specify	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
General disorders Fatigue	0.43% 7/1612 Participants at Risk includes any patient who submitted an AE form.	0.49% 8/1623 Participants at Risk includes any patient who submitted an AE form.
Blood and lymphatic system disorders Febrile neutropenia	0.43% 7/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
General disorders Fever	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Gastric hemorrhage	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Gastric ulcer	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Eye disorders Glaucoma	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Headache	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.43% 7/1623 Participants at Risk includes any patient who submitted an AE form.
Renal and urinary disorders Hematuria	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Hepatobiliary disorders Hepatic failure	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	0.62% 10/1612 Participants at Risk includes any patient who submitted an AE form.	0.55% 9/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Hot flashes	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Hyperglycemia	0.50% 8/1612 Participants at Risk includes any patient who submitted an AE form.	0.80% 13/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Hypertension	0.68% 11/1612 Participants at Risk includes any patient who submitted an AE form.	0.86% 14/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Hypoalbuminemia	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Hypokalemia	0.43% 7/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Hyponatremia	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Hypotension	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Ileus	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Infections and infestations Infections and infestations - Other, specify	1.7% 27/1612 Participants at Risk includes any patient who submitted an AE form.	1.7% 28/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations INR increased	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Psychiatric disorders Insomnia	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Intracranial hemorrhage	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Investigations - Other, specify	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Reproductive system and breast disorders Irregular menstruation	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Ischemia cerebrovascular	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Eye disorders Keratitis	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Lipase increased	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Lymphocyte count decreased	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Memory impairment	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Mucositis oral	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	0.50% 8/1612 Participants at Risk includes any patient who submitted an AE form.	0.43% 7/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Myalgia	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.37% 6/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Myocardial infarction	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Nervous system disorders - Other, specify	0.43% 7/1612 Participants at Risk includes any patient who submitted an AE form.	0.37% 6/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Neuralgia	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Neutrophil count decreased	4.5% 73/1612 Participants at Risk includes any patient who submitted an AE form.	6.6% 107/1623 Participants at Risk includes any patient who submitted an AE form.
General disorders Pain	0.43% 7/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Palpitations	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Pancreatitis	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Reproductive system and breast disorders Pelvic pain	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Pericardial effusion	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.12% 2/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Peripheral ischemia	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Peripheral motor neuropathy	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Peripheral sensory neuropathy	0.43% 7/1612 Participants at Risk includes any patient who submitted an AE form.	0.43% 7/1623 Participants at Risk includes any patient who submitted an AE form.
Psychiatric disorders Personality change	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Platelet count decreased	0.31% 5/1612 Participants at Risk includes any patient who submitted an AE form.	0.49% 8/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.12% 2/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.50% 8/1612 Participants at Risk includes any patient who submitted an AE form.	0.43% 7/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Skin and subcutaneous tissue disorders Pruritus	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Psychiatric disorders Psychosis	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.81% 13/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.12% 2/1623 Participants at Risk includes any patient who submitted an AE form.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Seizure	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Serum amylase increased	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Sinus bradycardia	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Sinus tachycardia	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Supraventricular tachycardia	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.55% 9/1623 Participants at Risk includes any patient who submitted an AE form.
Nervous system disorders Syncope	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Thromboembolic event	1.1% 18/1612 Participants at Risk includes any patient who submitted an AE form.	1.8% 30/1623 Participants at Risk includes any patient who submitted an AE form.
Renal and urinary disorders Urinary frequency	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Reproductive system and breast disorders Vaginal hemorrhage	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Vascular disorders - Other, specify	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Ventricular arrhythmia	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Eye disorders Watering eyes	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations Weight gain	0.19% 3/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Injury, poisoning and procedural complications Wound dehiscence	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Infections and infestations Wound infection	1.1% 17/1612 Participants at Risk includes any patient who submitted an AE form.	1.0% 17/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations White blood cell decreased	2.8% 45/1612 Participants at Risk includes any patient who submitted an AE form.	4.1% 66/1623 Participants at Risk includes any patient who submitted an AE form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Acute coronary syndrome	0.74% 12/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.31% 5/1623 Participants at Risk includes any patient who submitted an AE form.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Vascular disorders Visceral arterial ischemia	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Injury, poisoning and procedural complications Postoperative hemorrhage	0.00% 0/1612 Participants at Risk includes any patient who submitted an AE form.	0.06% 1/1623 Participants at Risk includes any patient who submitted an AE form.
Investigations GGT increased	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Injury, poisoning and procedural complications Dermatitis radiation	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Renal and urinary disorders Urinary tract obstruction	0.25% 4/1612 Participants at Risk includes any patient who submitted an AE form.	0.25% 4/1623 Participants at Risk includes any patient who submitted an AE form.
General disorders Non-cardiac chest pain	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.18% 3/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Ear and labyrinth disorders Middle ear inflammation	0.06% 1/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Musculoskeletal and connective tissue disorders Avascular necrosis	0.12% 2/1612 Participants at Risk includes any patient who submitted an AE form.	0.00% 0/1623 Participants at Risk includes any patient who submitted an AE form.
Cardiac disorders Left ventricular systolic dysfunction	0.37% 6/1612 Participants at Risk includes any patient who submitted an AE form.	0.37% 6/1623 Participants at Risk includes any patient who submitted an AE form.

Other adverse events

Measure	Clodronate n=1612 participants at risk Clodronate	Placebo n=1623 participants at risk Placebo
Investigations Neutrophil count decreased	4.5% 73/1612 Participants at Risk includes any patient who submitted an AE form.	6.6% 107/1623 Participants at Risk includes any patient who submitted an AE form.

Additional Information

Director, Department of Regulatory Affairs

NSABP Foundation, Inc.

Phone: 412-339-5300

Email: regulatory@nsabp.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60