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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01712009
Other study ID # 20110147
Secondary ID
Status Completed
Phase Phase 2
First received October 19, 2012
Last updated January 5, 2018
Start date November 1, 2012
Est. completion date March 18, 2015

Study information

Verified date January 2018
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 600
Est. completion date March 18, 2015
Est. primary completion date March 18, 2015
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 100 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Naproxen

Loratadine

Biological:
Pegfilgrastim
Commercially available pegfilgrastim (Neulasta®) will be used in the study, and is considered background therapy. Pegfilgrastim is administered as a single 6 mg subcutaneous injection 24 hours to 72 hours after completion of chemotherapy.
Drug:
Chemotherapy
The choice of chemotherapy regimen (agent, dose, and schedule) is at the discretion of the treating physician.

Locations

Country Name City State
United States Research Site Alexandria Louisiana
United States Research Site Anaheim California
United States Research Site Augusta Georgia
United States Research Site Battle Creek Michigan
United States Research Site Bend Oregon
United States Research Site Bethlehem Pennsylvania
United States Research Site Billings Montana
United States Research Site Boynton Beach Florida
United States Research Site Bristol Tennessee
United States Research Site Chattanooga Tennessee
United States Research Site Chesapeake Virginia
United States Research Site Corpus Christi Texas
United States Research Site Corpus Christi Texas
United States Research Site Cumberland Maryland
United States Research Site Daytona Beach Florida
United States Research Site Daytona Beach Florida
United States Research Site Denver Colorado
United States Research Site Denville New Jersey
United States Research Site Duluth Minnesota
United States Research Site East Syracuse New York
United States Research Site Elmhurst Illinois
United States Research Site Florence South Carolina
United States Research Site Fort Lauderdale Florida
United States Research Site Fullerton California
United States Research Site Gastonia North Carolina
United States Research Site Golden Colorado
United States Research Site Gurnee Illinois
United States Research Site Hickory North Carolina
United States Research Site Huntington West Virginia
United States Research Site Hutchinson Kansas
United States Research Site Indianapolis Indiana
United States Research Site Jackson Mississippi
United States Research Site Janesville Wisconsin
United States Research Site Jefferson City Missouri
United States Research Site Johnson City New York
United States Research Site Kansas City Missouri
United States Research Site Lafayette Louisiana
United States Research Site Lakeland Florida
United States Research Site Langhorne Pennsylvania
United States Research Site Lexington Kentucky
United States Research Site Littleton Colorado
United States Research Site Louisville Kentucky
United States Research Site Lowell Massachusetts
United States Research Site Madison Wisconsin
United States Research Site Marrero Louisiana
United States Research Site Massillon Ohio
United States Research Site Mount Sterling Kentucky
United States Research Site Mount Vernon Illinois
United States Research Site Muscle Shoals Alabama
United States Research Site Nashua New Hampshire
United States Research Site New Port Richey Florida
United States Research Site Norwich Connecticut
United States Research Site Ogden Utah
United States Research Site Omaha Nebraska
United States Research Site Paducah Kentucky
United States Research Site Pinehurst North Carolina
United States Research Site Plano Texas
United States Research Site Plantation Florida
United States Research Site Racine Wisconsin
United States Research Site Randallstown Maryland
United States Research Site Rockville Maryland
United States Research Site Saint Cloud Minnesota
United States Research Site Saint Joseph Missouri
United States Research Site Saint Louis Missouri
United States Research Site Santa Maria California
United States Research Site Santa Rosa California
United States Research Site Shreveport Louisiana
United States Research Site Sioux City Iowa
United States Research Site Skokie Illinois
United States Research Site South Bend Indiana
United States Research Site Spokane Washington
United States Research Site Stamford Connecticut
United States Research Site Stuart Florida
United States Research Site Thomasville Georgia
United States Research Site Torrance California
United States Research Site Urbana Illinois
United States Research Site Waterloo Iowa
United States Research Site Watertown South Dakota
United States Research Site Wauwatosa Wisconsin
United States Research Site Westminster Maryland
United States Research Site Weston Wisconsin
United States Research Site Whittier California
United States Research Site Zanesville Ohio

Sponsors (1)

Lead Sponsor Collaborator
Amgen

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. 2017 Nov 16. doi: 10.1007/s00520-017-3959-2. [Epub ahead of print] — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With Bone Pain (All Grades) in Cycle 1 Bone pain data were captured as part of standard adverse event (AE) reporting. Cycle 1 (approximately 4 weeks, depending on the chemotherapy dosing interval)
Secondary Percentage of Participants With Bone Pain (All Grades) by Cycle (2-4) and Across Cycles Bone pain data were captured as part of standard adverse event (AE) reporting. Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval)
Secondary Percentage of Participants With Severe Bone Pain by Cycle and Across Cycles 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. Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval)
Secondary Mean Patient-reported Bone Pain by Cycle and Across Cycles 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. Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)
Secondary Maximum Patient-reported Bone Pain by Cycle and Across Cycles 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. Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)
Secondary Area Under the Curve (AUC) for Patient-reported Bone Pain 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. Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle)
Secondary Number of Participants With Adverse Events (AEs) 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.
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.