NOLAN: Naproxen or Loratadine and Neulasta

Phase 2

Completed

Conditions: Bone Pain in Stage I - III Breast Cancer

Interventions: Drug: Loratadine
Drug: Naproxen
Biological: Pegfilgrastim
Drug: Chemotherapy

Registration Number: NCT01712009

Lead Sponsor: Amgen

Brief Summary: The primary objective of the study is to estimate the difference in bone pain between breast cancer patients receiving chemotherapy and pegfilgrastim and either no prophylactic intervention, prophylactic naproxen, or prophylactic loratadine.

Detailed Description: In this study, the investigational products are naproxen, a non-steroidal antiinflammatory drug (NSAID), and loratadine, an anti-histamine. Both agents are being investigated as prophylactic medications to reduce the incidence and/or severity of bone pain in breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy and pegfilgrastim prophylaxis.

Pegfilgrastim treatment is used to stimulate bone marrow to produce more neutrophils to help fight infections in patients undergoing chemotherapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 600

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylactic naproxen	Pegfilgrastim	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic naproxen 500 mg orally twice a day (BID) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.
Prophylactic naproxen	Chemotherapy	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic naproxen 500 mg orally twice a day (BID) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.
No prophylactic treatment	Pegfilgrastim	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis.
No prophylactic treatment	Chemotherapy	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis.
Prophylactic loratadine	Pegfilgrastim	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic loratadine 10 mg once a day (QD) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.
Prophylactic loratadine	Chemotherapy	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic loratadine 10 mg once a day (QD) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.
Prophylactic loratadine	Loratadine	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic loratadine 10 mg once a day (QD) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.
Prophylactic naproxen	Naproxen	Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic naproxen 500 mg orally twice a day (BID) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Bone Pain (All Grades) in Cycle 1	Cycle 1 (approximately 4 weeks, depending on the chemotherapy dosing interval)	Bone pain data were captured as part of standard adverse event (AE) reporting.

Secondary Outcome Measures

Name	Time	Method
Maximum Patient-reported Bone Pain by Cycle and Across Cycles	Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)	Participants completed a brief bone pain survey once per day for 5 days beginning the day they received their pegfilgrastim injection. The bone pain survey collected the severity of pain using a 0 (no pain) to 10 (worst pain) scale. Maximum patient-reported bone pain is the maximum of each participant's bone pain values across survey Days 1-5 within each cycle. Across all cycles the maximum is the maximum of each patient-reported bone pain value across all survey days 1-5 and across all cycles. An ANOVA model with treatment as explanatory term was used.
Percentage of Participants With Bone Pain (All Grades) by Cycle (2-4) and Across Cycles	Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval)	Bone pain data were captured as part of standard adverse event (AE) reporting.
Area Under the Curve (AUC) for Patient-reported Bone Pain	Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)	Patient-reported bone pain AUC was calculated using the trapezoidal rule with bone pain scores from day 1 to 5 for each cycle. The AUC across cycles is the average of AUCs across the cycle.
Number of Participants With Adverse Events (AEs)	From first dose of investigational product (IP, naproxen or loratidine) or first dose of pegfilgrastim (Peg), whichever occurred first, until 30 days after last dose, up to 24 weeks.	Severity was graded using CTCAE version 3. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal; • life threatening; • requires in-patient hospitalization or prolongation of existing hospitalization; • results in persistent or significant disability/incapacity; • congenital anomaly/birth defect; • other medically important serious event. The investigator assessed each adverse event for relatedness to investigational product(s) or other protocol-required therapies.
Percentage of Participants With Severe Bone Pain by Cycle and Across Cycles	Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval)	Bone pain data were captured as part of standard adverse event reporting. Severe bone pain is defined as grade 3 or 4 according to common terminology criteria for adverse events (CTCAE) version 3 grading criteria: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, and Grade 4 = Life-threatening or disabling.
Mean Patient-reported Bone Pain by Cycle and Across Cycles	Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)	Participants completed a brief bone pain survey once per day for 5 days beginning the day they received their pegfilgrastim injection. The bone pain survey collected the severity of pain using a 0 (no pain) to 10 (worst pain) scale. Mean patient-reported bone pain values are the average of each participant's bone pain values across survey days 1-5 within each cycle. Across all cycles the mean is the average of each patient-reported bone pain value across all survey days 1-5 and across all cycles. An analysis of variance (ANOVA) model with treatment as explanatory term was used.