Clinical trial NCT01712009: NOLAN: Naproxen or Loratadine and Neulasta
Official title: Randomized, Phase 2 Study to Estimate the Effect of Prophylactic Intervention With Naproxen or Loratadine on Bone Pain in Breast Cancer Subjects Receiving Chemotherapy and Pegfilgrastim
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bone Pain in Stage I - III Breast Cancer
Keywords: Breast cancer
Chemotherapy
Neulasta
Pegfilgrastim
Naproxen
Loratadine
Non-steroidal antiinflammatory drug (NSAID)
Anti-histamine
Bone Pain
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-10-23
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Age 18 years or over

* Eastern cooperative oncology group (ECOG) performance status 0-2
* Female with newly diagnosed, not previously treated with chemotherapy, stage I-III breast cancer
* Medically eligible to safely receive adjuvant or neoadjuvant chemotherapy, pegfilgrastim, naproxen and loratadine as determined by the investigator
* Creatinine ≤ 1.5 X upper limit of normal (ULN)
* Planning to receive at least 4 cycles of adjuvant or neoadjuvant chemotherapy
* Planning to receive prophylaxis with pegfilgrastim starting in the first cycle and continuing throughout each chemotherapy cycle of the treatment period
* Subject has provided informed consent

Exclusion Criteria

* History of other malignancy within the past 5 years, with the following exceptions:

  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  * Adequately treated cervical carcinoma in situ without evidence of disease
* Planning to receive weekly chemotherapy
* Ongoing chronic pain, or other painful conditions requiring treatment (including immediate post-operative treatment of surgical or procedural-associated pain) as determined by the investigator
* Chronic oral steroid use. Premedication related to the administration of chemotherapy, and use of anti-emetics is allowed, per usual clinical practice
* Chronic use of oral non-steroidal anti-inflammatory drug (NSAIDs) or oral antihistamines outside of those dictated by the randomization groups outlined in the protocol, with the following exception:

  - Chronic oral aspirin use for cardiovascular-related indications
* Prior chemotherapy treatment for cancer within 5 years of current breast cancer diagnosis
* Prior use of granulocyte colony stimulating factor (G-CSF)
* History of clinically significant gastrointestinal (GI) bleeding, history of GI ulcers or active GI bleeding within 6 months prior to randomization
* History of clinically significant bleeding disorders, thromboembolism within 6 months prior to randomization
* Currently enrolled in, or less than 30 days since ending, another clinical trial which includes language directing G-CSF (filgrastim, pegfilgrastim, other) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim) use
* Currently enrolled in, or less than 30 days since ending, another interventional clinical trial which includes a blinded treatment or blinded treatment arm (whether or not the subject is randomized to the blinded arm)
* Currently enrolled in, or less than 30 days since ending, another interventional clinical trial which includes the use of any agent not currently considered to be standard therapy for the adjuvant or neoadjuvant treatment of stage I-III breast cancer based on National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Breast Cancer
* Currently enrolled in, or less than 30 days since ending, any pain intervention study
* Female subjects who are pregnant or lactating or of reproductive potential not willing to employ an effective method of birth control during treatment and for 17 days after discontinuing study treatment
* History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

Primary outcomes:
measure: Percentage of Participants With Bone Pain (All Grades) in Cycle 1
timeFrame: Cycle 1 (approximately 4 weeks, depending on the chemotherapy dosing interval)
Secondary outcomes:
measure: Percentage of Participants With Bone Pain (All Grades) by Cycle (2-4) and Across Cycles
timeFrame: Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval)
measure: Percentage of Participants With Severe Bone Pain by Cycle and Across Cycles
timeFrame: Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval)
measure: Mean Patient-reported Bone Pain by Cycle and Across Cycles
timeFrame: Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)
measure: Maximum Patient-reported Bone Pain by Cycle and Across Cycles
timeFrame: Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)
measure: Area Under the Curve (AUC) for Patient-reported Bone Pain
timeFrame: Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Research Site
state: Alabama
city: Anaheim
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: Santa Maria
country: United States
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state: California
city: Santa Rosa
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state: California
city: Torrance
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state: California
city: Whittier
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state: California
city: Denver
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state: Colorado
city: Golden
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state: Colorado
city: Littleton
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state: Colorado
city: Norwich
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state: Connecticut
city: Stamford
country: United States
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state: Connecticut
city: Boynton Beach
country: United States
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state: Florida
city: Daytona Beach
country: United States
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state: Florida
city: Daytona Beach
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state: Florida
city: Fort Lauderdale
country: United States
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state: Florida
city: Lakeland
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state: Florida
city: New Port Richey
country: United States
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state: Florida
city: Plantation
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state: Florida
city: Stuart
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state: Florida
city: Augusta
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state: Georgia
city: Thomasville
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state: Georgia
city: Elmhurst
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state: Illinois
city: Gurnee
country: United States
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state: Illinois
city: Mount Vernon
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state: Illinois
city: Skokie
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state: Illinois
city: Urbana
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state: Illinois
city: Indianapolis
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state: Indiana
city: South Bend
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state: Indiana
city: Sioux City
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state: Iowa
city: Waterloo
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state: Iowa
city: Hutchinson
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state: Kansas
city: Lexington
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state: Kentucky
city: Louisville
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state: Kentucky
city: Mount Sterling
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state: Kentucky
city: Paducah
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state: Kentucky
city: Alexandria
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state: Louisiana
city: Lafayette
country: United States
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state: Louisiana
city: Marrero
country: United States
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state: Louisiana
city: Shreveport
country: United States
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state: Louisiana
city: Cumberland
country: United States
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state: Maryland
city: Randallstown
country: United States
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state: Maryland
city: Rockville
country: United States
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state: Maryland
city: Westminster
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state: Maryland
city: Lowell
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state: Massachusetts
city: Battle Creek
country: United States
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state: Michigan
city: Duluth
country: United States
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state: Minnesota
city: Saint Cloud
country: United States
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state: Minnesota
city: Jackson
country: United States
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state: Mississippi
city: Jefferson City
country: United States
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state: Missouri
city: Kansas City
country: United States
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state: Missouri
city: Saint Joseph
country: United States
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state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Billings
country: United States
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state: Montana
city: Omaha
country: United States
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state: Nebraska
city: Nashua
country: United States
facility: Research Site
state: New Hampshire
city: Denville
country: United States
facility: Research Site
state: New Jersey
city: East Syracuse
country: United States
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state: New York
city: Johnson City
country: United States
facility: Research Site
state: New York
city: Gastonia
country: United States
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state: North Carolina
city: Hickory
country: United States
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state: North Carolina
city: Pinehurst
country: United States
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state: North Carolina
city: Massillon
country: United States
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state: Ohio
city: Zanesville
country: United States
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state: Ohio
city: Bend
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state: Oregon
city: Bethlehem
country: United States
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state: Pennsylvania
city: Langhorne
country: United States
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state: Pennsylvania
city: Florence
country: United States
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state: South Carolina
city: Watertown
country: United States
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state: South Dakota
city: Bristol
country: United States
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state: Tennessee
city: Chattanooga
country: United States
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state: Tennessee
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Plano
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
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state: Utah
city: Chesapeake
country: United States
facility: Research Site
state: Virginia
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Huntington
country: United States
facility: Research Site
state: West Virginia
city: Janesville
country: United States
facility: Research Site
state: Wisconsin
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Racine
country: United States
facility: Research Site
state: Wisconsin
city: Wauwatosa
country: United States
facility: Research Site
state: Wisconsin
city: Weston
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kirshner JJ, McDonald MC 3rd, Kruter F, Guinigundo AS, Vanni L, Maxwell CL, Reiner M, Upchurch TE, Garcia J, Morrow PK. NOLAN: a randomized, phase 2 study to estimate the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on bone pain in patients with early-stage breast cancer receiving chemotherapy and pegfilgrastim. Support Care Cancer. 2018 Apr;26(4):1323-1334. doi: 10.1007/s00520-017-3959-2. Epub 2017 Nov 16.