Musculoskeletal Complications, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
pain, musculoskeletal complications, unspecified adult solid tumor, protocol specific
Brief summary
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.
Detailed description
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.
Interventions
DRUGnaproxen
Oral naproxen twice daily for 5-8 days.
OTHERplacebo
Oral placebo twice daily for 5-8 days.
Sponsors
National Cancer Institute (NCI)
Gary Morrow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve (AUC) of Average Pain From Diary vs. Day (1-5), Calculated by the Trapezoidal Rule. | From baseline through day 5 | Severity and duration of bone pain (day 1 being the day pegfilgrastim is administered) as measured by a daily diary. Patients recorded daily pain (Pain Scale Score) severity on a scale of 0 (no pain) to 10 (pain as bad as you can imagine) for the last 24 hours. The AUC range was 0-40, and the units are (Pain Scale Score)\*Days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naproxen Patients receive oral naproxen twice daily beginning on the day pegfilgrastim is administered (day 2, 3, or 4) and continuing for 5-8 days.
naproxen: Oral naproxen twice daily for 5-8 days. | 257 |
| Placebo Patients receive an oral placebo twice daily beginning on the day pegfilgrastim is administered (day 2, 3, or 4) and continuing for 5-8 days.
placebo: Oral placebo twice daily for 5-8 days. | 253 |
| Total | 510 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Chemotoxicity, Inc. Data,Ineligible | 5 | 3 |
| Overall Study | Death | 1 | 4 |
| Overall Study | Withdrawal by Subject | 18 | 17 |
Baseline characteristics
| Characteristic | Naproxen | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 12.8 | 56.8 years STANDARD_DEVIATION 11.1 | 56.2 years STANDARD_DEVIATION 12 |
| Bone pain today or during previous 3 days (scale, 0-10) | 0.47 units on a scale STANDARD_DEVIATION 1.44 | 0.64 units on a scale STANDARD_DEVIATION 1.6 | 0.56 units on a scale STANDARD_DEVIATION 1.52 |
| Education High school or less | 73 participants | 87 participants | 160 participants |
| Education Other | 4 participants | 2 participants | 6 participants |
| Education Some college | 180 participants | 164 participants | 344 participants |
| Marital Status Married | 181 participants | 179 participants | 360 participants |
| Marital Status Not Married | 72 participants | 72 participants | 144 participants |
| Marital Status Unknown | 4 participants | 2 participants | 6 participants |
| Pain at its worst in last 24 hours (scale, 0-10) | 1.78 units on a scale STANDARD_DEVIATION 2.24 | 1.87 units on a scale STANDARD_DEVIATION 2.23 | 1.83 units on a scale STANDARD_DEVIATION 2.24 |
| Previous chemotherapy No | 193 participants | 176 participants | 369 participants |
| Previous chemotherapy Unknown | 4 participants | 2 participants | 6 participants |
| Previous chemotherapy Yes | 60 participants | 75 participants | 135 participants |
| Previous Radiation Therapy No | 235 participants | 221 participants | 456 participants |
| Previous Radiation Therapy Unknown | 4 participants | 2 participants | 6 participants |
| Previous Radiation Therapy Yes | 18 participants | 30 participants | 48 participants |
| Previous tamoxifen No | 245 participants | 240 participants | 485 participants |
| Previous tamoxifen Unknown | 4 participants | 2 participants | 6 participants |
| Previous tamoxifen Yes | 8 participants | 11 participants | 19 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 19 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) White | 228 Participants | 227 Participants | 455 Participants |
| Region of Enrollment United States | 257 participants | 253 participants | 510 participants |
| Sex: Female, Male Female | 222 Participants | 215 Participants | 437 Participants |
| Sex: Female, Male Male | 35 Participants | 38 Participants | 73 Participants |
| Tumor Type Breast | 175 participants | 166 participants | 341 participants |
| Tumor Type Gynecologic | 16 participants | 13 participants | 29 participants |
| Tumor Type Hematologic | 18 participants | 17 participants | 35 participants |
| Tumor Type Lung | 22 participants | 31 participants | 53 participants |
| Tumor Type Other | 26 participants | 26 participants | 52 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 257 | 3 / 253 |
| serious Total, serious adverse events | 5 / 257 | 3 / 253 |
Outcome results
Primary
Area Under Curve (AUC) of Average Pain From Diary vs. Day (1-5), Calculated by the Trapezoidal Rule.
Severity and duration of bone pain (day 1 being the day pegfilgrastim is administered) as measured by a daily diary. Patients recorded daily pain (Pain Scale Score) severity on a scale of 0 (no pain) to 10 (pain as bad as you can imagine) for the last 24 hours. The AUC range was 0-40, and the units are (Pain Scale Score)\*Days.
Time frame: From baseline through day 5
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Naproxen | Area Under Curve (AUC) of Average Pain From Diary vs. Day (1-5), Calculated by the Trapezoidal Rule. | 6.04 (Pain Scale Score)*Days |
| Placebo | Area Under Curve (AUC) of Average Pain From Diary vs. Day (1-5), Calculated by the Trapezoidal Rule. | 7.71 (Pain Scale Score)*Days |
Comparison: Tested at the two-sided 0.05 significance level.p-value: 0.03795% CI: [0.1, 3.24]t-test, 2 sided
Comparison: Tested at the two-sided 0.05 significance level.p-value: 0.007Wilcoxon (Mann-Whitney)