NOLAN: Naproxen or Loratadine and Neulasta (NOLAN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01712009
First received: October 19, 2012
Last updated: February 9, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Bone Pain in Stage I - III Breast Cancer
Drug: Naproxen
Drug: Loratadine
Biological: Pegfilgrastim
Drug: Chemotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Participants With Bone Pain (All Grades) in Cycle 1 [ Time Frame: Cycle 1 (approximately 4 weeks, depending on the chemotherapy dosing interval) ] [ Designated as safety issue: No ]
    Bone pain data were captured as part of standard adverse event (AE) reporting.


Secondary Outcome Measures:
  • Percentage of Participants With Bone Pain (All Grades) by Cycle (2-4) and Across Cycles [ Time Frame: Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval) ] [ Designated as safety issue: No ]
    Bone pain data were captured as part of standard adverse event (AE) reporting.

  • Percentage of Participants With Severe Bone Pain by Cycle and Across Cycles [ Time Frame: Cycles 1, 2, 3 and 4 (approximately 4 weeks each, depending on the chemotherapy dosing interval) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle) ] [ Designated as safety issue: No ]
    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.

  • Maximum Patient-reported Bone Pain by Cycle and Across Cycles [ Time Frame: Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle) ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve (AUC) for Patient-reported Bone Pain [ Time Frame: Five consecutive days during each cycle beginning on the day of pegfilgrastim administration (Day 2, 3, or 4 of each cycle) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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. ] [ Designated as safety issue: No ]

    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.



Enrollment: 600
Study Start Date: November 2012
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prophylactic 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.
Drug: Naproxen 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.
Other Name: Neulasta®
Drug: Chemotherapy
The choice of chemotherapy regimen (agent, dose, and schedule) is at the discretion of the treating physician.
Experimental: Prophylactic 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.
Drug: 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.
Other Name: Neulasta®
Drug: Chemotherapy
The choice of chemotherapy regimen (agent, dose, and schedule) is at the discretion of the treating physician.
No prophylactic treatment
Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis.
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.
Other Name: Neulasta®
Drug: Chemotherapy
The choice of chemotherapy regimen (agent, dose, and schedule) is at the discretion of the treating physician.

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

Ages Eligible for Study:   18 Years to 100 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01712009

  Show 83 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01712009     History of Changes
Other Study ID Numbers: 20110147 
Study First Received: October 19, 2012
Results First Received: February 9, 2016
Last Updated: February 9, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Amgen:
Breast cancer
Chemotherapy
Neulasta
Pegfilgrastim
Naproxen
Loratadine
Non-steroidal antiinflammatory drug (NSAID)
Anti-histamine
Bone Pain

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Anti-Inflammatory Agents, Non-Steroidal
Loratadine
Naproxen
Analgesics
Analgesics, Non-Narcotic
Anti-Allergic Agents
Anti-Inflammatory Agents
Antipruritics
Antirheumatic Agents
Cyclooxygenase Inhibitors
Dermatologic Agents
Enzyme Inhibitors
Gout Suppressants
Histamine Agents
Histamine Antagonists
Histamine H1 Antagonists
Histamine H1 Antagonists, Non-Sedating
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on May 23, 2016