Trial Outcomes & Findings for Leuprorelin Acetate SR 11.25 mg for Injection Specified Drug-use Survey "Long-term Use Survey on Premenopausal Breast Cancer Patients (96 Weeks)" (NCT NCT02154139)

Last Updated: 2016-02-17

Results Overview

Adverse drug reactions are defined as adverse events (AE) which are in the investigator's opinion of causal relationship to the study treatment. AE are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

Recruitment status

COMPLETED

Target enrollment

651 participants

Primary outcome timeframe

Baseline up to 96 weeks

Results posted on

2016-02-17

Participant Flow

Participants took part in the study at 157 investigative site in Japan from 26-Dec-05 to 31-Mar-10.

Participants with a historical diagnosis of premenopausal breast cancer (advanced or recurrent) who were treated with Leuprorelin Acetate 11.25 milligrams (mg) in daily medical practice along with adjuvant therapy were observed.

Participant milestones

Participant milestones
Measure	Leuprorelin Acetate Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Overall Study STARTED	651
Overall Study COMPLETED	644
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Leuprorelin Acetate Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Overall Study Injection not administered	2
Overall Study Other	2
Overall Study Investigator transferred	3

Baseline Characteristics

Leuprorelin Acetate SR 11.25 mg for Injection Specified Drug-use Survey "Long-term Use Survey on Premenopausal Breast Cancer Patients (96 Weeks)"

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Leuprorelin Acetate n=644 Participants Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Age, Customized 20-29 years	11 participants n=99 Participants
Age, Customized 30-34 years	47 participants n=99 Participants
Age, Customized 35-39 years	113 participants n=99 Participants
Age, Customized 40-44 years	201 participants n=99 Participants
Age, Customized 45-49 years	212 participants n=99 Participants
Age, Customized 50-55 years	58 participants n=99 Participants
Age, Customized Unknown	2 participants n=99 Participants
Sex/Gender, Customized	644 participants n=99 Participants
Stage of primary lesion T0N0M0	2 participants n=99 Participants
Stage of primary lesion Stage 0	17 participants n=99 Participants
Stage of primary lesion Stage I	265 participants n=99 Participants
Stage of primary lesion Stage IIA	199 participants n=99 Participants
Stage of primary lesion Stage IIB	85 participants n=99 Participants
Stage of primary lesion Stage IIIA	24 participants n=99 Participants
Stage of primary lesion Stage IIIB	6 participants n=99 Participants
Stage of primary lesion Stage IIIC	1 participants n=99 Participants
Stage of primary lesion Stage IV	23 participants n=99 Participants
Stage of primary lesion Unclassifiable	22 participants n=99 Participants
Recurrence prior to start of treatment with leuprorelin acetate 11.25 mg for injection Experienced recurrence	50 participants n=99 Participants
Recurrence prior to start of treatment with leuprorelin acetate 11.25 mg for injection No recurrence observed	594 participants n=99 Participants
Performance Status (at the start of treatment with leuprorelin acetate 11.25 mg for injection) 0	602 participants n=99 Participants
Performance Status (at the start of treatment with leuprorelin acetate 11.25 mg for injection) 1	33 participants n=99 Participants
Performance Status (at the start of treatment with leuprorelin acetate 11.25 mg for injection) 2	3 participants n=99 Participants
Performance Status (at the start of treatment with leuprorelin acetate 11.25 mg for injection) 3	4 participants n=99 Participants
Performance Status (at the start of treatment with leuprorelin acetate 11.25 mg for injection) 4	2 participants n=99 Participants

PRIMARY outcome

Timeframe: Baseline up to 96 weeks

Population: Safety analysis set was defined as participants who were enrolled and completed the study.

Outcome measures

Outcome measures
Measure	Leuprorelin Acetate n=644 Participants Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Number of Participants Reporting One or More Adverse Drug Reactions	128 participants

PRIMARY outcome

Timeframe: Baseline up to 96 weeks

Population: Safety analysis set was defined as participants who were enrolled and completed the study.

Serious adverse drug reactions are defined as serious adverse events (SAE) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The event occurred was breast cancer female

Outcome measures

Outcome measures
Measure	Leuprorelin Acetate n=644 Participants Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Number of Participants Reporting One or More Serious Adverse Drug Reactions	1 participants

SECONDARY outcome

Timeframe: Week 24, 48,96

Population: The efficacy assessment population was defined as participants with advanced or recurrent breast cancer whose efficacy data at baseline and at least 1 post-baseline time points was available.

Best overall response for a participant is the best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions greater than or equal to (\>=) 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of \>= 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Leuprorelin Acetate n=48 Participants Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Percentage of Participants With Advanced or Recurrent Breast Cancer (Best Response) Week 24	10.34 percentage of participants Interval 2.19 to 27.35
Percentage of Participants With Advanced or Recurrent Breast Cancer (Best Response) Week 48	12.00 percentage of participants Interval 2.55 to 31.22
Percentage of Participants With Advanced or Recurrent Breast Cancer (Best Response) Week 96	15.00 percentage of participants Interval 3.21 to 37.89

SECONDARY outcome

Timeframe: Baseline up to 96 weeks

Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.

Outcome measures

Outcome measures
Measure	Leuprorelin Acetate n=44 Participants Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Percentage of Participants With Progression Free Survival	49.68 percentage of participants Interval 32.47 to 64.73

SECONDARY outcome

Timeframe: Baseline up to 96 weeks

Recurrence-free survival was determined in participants who were treated with the drug as adjuvant therapy, and tabulated, based on the date recurrence is confirmed, the presence or absence of recurrence, continued survival or death, and the date of death.

Outcome measures

Outcome measures
Measure	Leuprorelin Acetate n=522 Participants Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
Percentage of Participants With Recurrence-free Survival Who Were Treated With the Drug as Adjuvant Therapy	95.37 percentage of participants Interval 92.96 to 96.96

Adverse Events

Leuprorelin Acetate

Serious events: 20 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Leuprorelin Acetate n=644 participants at risk Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
General disorders Condition aggravated	0.47% 3/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood amylase increased	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Carbohydrate antigen 15-3 increased	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Urine amylase increased	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Completed suicide	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Schizophrenia	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	1.4% 9/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian neoplasm	0.31% 2/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Pancreatitis acute	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Radiation pneumonitis	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Leukopenia	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Granulocytopenia	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac tamponade	0.16% 1/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	Leuprorelin Acetate n=644 participants at risk Leuprorelin Acetate 11.25 mg, injection subcutaneously once every 12 weeks up to 96 weeks.
General disorders Injection site induration	6.4% 41/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hot flush	5.4% 35/644 • Baseline up to 96 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER