Prevention of Pegfilgrastim-Induced Bone Pain (PIBP)

Prevention of Pegfilgrastim-Induced Bone Pain (PIBP): A Phase III Double-Blind Placebo-Controlled Clinical Trial

RATIONALE: Naproxen may help prevent or lessen bone pain caused by pegfilgrastim. It is not yet known whether naproxen is more effective than a placebo in preventing bone pain caused by pegfilgrastim in patients with non-hematologic cancer undergoing chemotherapy.

PURPOSE: This randomized phase III trial is studying naproxen to see how well it works compared with a placebo in preventing bone pain caused by pegfilgrastim in patients with non-hematologic cancer undergoing chemotherapy.

OBJECTIVES:

Primary

• To compare the efficacy of daily administration of naproxen vs placebo in preventing or reducing the severity and duration of pegfilgrastim-induced bone pain (PIBP) in patients with non-hematologic malignancies undergoing chemotherapy.

Secondary

• To identify potential risk factors for the development of PIBP.
• To identify potential clinical predictors for the response or failure to respond to naproxen in preventing PIBP.
• To assess the toxicity of naproxen when administered in the preventive setting.

OUTLINE: This is a multicenter study. Patients are stratified by Clinical Community Oncology Program (CCOP) site. Patients are randomized to 1 treatment arm vs placebo.

• Arm I: Patients receive oral naproxen twice daily beginning on the day pegfilgrastim is administered (day 2, 3, or 4) and continuing for 5-8 days.
• Arm II: Patients receive matching placebo twice daily beginning on the day pegfilgrastim is administered (day 2, 3, or 4) and continuing for 5-8 days.

Inclusion Criteria:

• Diagnosis of a non-hematologic (non-myeloid) malignancy
• Scheduled to receive chemotherapy; chemotherapy may be given for adjuvant, neoadjuvant, curative, or palliative intent
• Scheduled to receive the first dose of pegfilgrastim (Neulasta®) to ameliorate chemotherapy-induced neutropenia
• Creatinine ≤ 1.5 times upper limit of normal
• Able to understand English
• More than 6 months since prior surgery on the heart

Exclusion Criteria:

• Pregnant or nursing
• Clinical evidence of active gastrointestinal bleeding, prior gastrointestinal bleeding, or gastric or duodenal ulcers
• Allergy to naproxen
• Prior development of the triad of asthma, rhinitis, and nasal polyps after taking acetylsalicylic acid (aspirin) or other NSAIDs
• Concurrent nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or any product containing naproxen (e.g., Naprosyn, EC-Naprosyn, Anaprox, Anaprox-DS, Naprosyn suspension, or Aleve), on a regular basis
• Concurrent steroids on a regular basis
• Concurrent prescription or non-prescription medications for preexisting chronic pain; concurrent cardioprotective doses (≤ 325 mg/day) of aspirin allowed
• Concurrent therapeutic doses of warfarin