Omega-3 Fatty Acid in Treating Pain in Patients With Breast or Ovarian Cancer Receiving Paclitaxel

Sponsor

New Mexico Cancer Care Alliance (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01821833

Collaborator

Alliance Healthcare Foundation (Other)

Enrollment

Locations

Arms

86.2

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Paclitaxel, a widely used chemotherapeutic agent, is associated with several well-known side effects including neuropathy (weakness, numbness and pain) and generalized body aches. The latter has recently been described as paclitaxel-associated acute pain syndrome (P-APS) and often occurs in the first three to four days after administration. It affects about 58-90% of patients. Currently, the mechanism of P-APS is unknown, and there is no standard of care to treat it. However, an intervention with both anti-inflammatory as well as neuroprotective properties would be an ideal candidate for testing in the prevention of P-APS and subsequent development of peripheral neuropathy. Previous studies have suggested that omega-3 fatty acids may act as neuroprotective agents, and there are no currently documented safety concerns with their combined use with paclitaxel.

Therefore, this randomized pilot clinical trial will determine whether omega-3 fatty acids can treat pain in patients with breast or ovarian cancer receiving paclitaxel.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Ovarian Neoplasm Pain	Dietary Supplement: Omega-3 fatty acid Dietary Supplement: Placebo Drug: Paclitaxel	N/A

Detailed Description

One mechanism proposed for P-APS is an early inflammatory process characterized by macrophage activation in both the dorsal root ganglia and peripheral nerve occurring shortly after paclitaxel therapy. Morphologic alterations in DRG satellite cells have been noted and upregulation of proinflammatory cytokines have been hypothesized as early events in the development of neuropathy. Therefore, it is possible that paclitaxel-induced neuropathic pain may be mediated by pro-inflammatory cytokines. If P-APS and chronic neuropathy are indeed part of a continuum, the inflammatory pathway would be a reasonable target for therapy. While the mechanism of how paclitaxel leads to the development of neuropathy is still not understood, it has been hypothesized that its microtubule-stabilizing effects disrupt axonal transport. Intervention with an agent that is both anti-inflammatory as well as neuroprotective is therefore worth exploring.

Long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are common dietary supplements. They have well established anti-inflammatory properties which serve as the basis for their use in therapeutic trials in inflammatory conditions. Omega -3 fatty acids consumption can attenuate the production of pro-inflammatory metabolites. In addition, it can generate local mediators that facilitate resolution of inflammation. Thus, if P-APS is indeed mediated by inflammation, the anti-inflammatory activity of omega 3 fatty acids may be one mechanism to prevent P-APS. Additionally, given its well established safety profile, it may be an attractive alternative to NSAIDS.

A dose of at least 2.7 g/day of EPA and DHA have been reported to have analgesic effects in inflammatory conditions. The dose of 4 g/day is an FDA-approved dose of omega 3 fatty acids (Lovaza) for the treatment of hypertriglyceridemia and has a well-documented toxicity profile. On the basis of this, a dose of 4 g/day was selected for this study. Lovaza (omega-3-acid ethyl esters) capsules will be used. Each 1-gram capsule contains approximately 465 mg EPA and 375 mg DHA.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

A Pilot Randomized, Placebo Controlled, Double Blind Study of Omega-3 Fatty Acids to Prevent Paclitaxel Associated Acute Pain Syndrome

Actual Study Start Date :

May 24, 2016

Actual Primary Completion Date :

Jan 16, 2018

Anticipated Study Completion Date :

Jul 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (Omega-3 fatty acid) Four Omega-3 fatty acid capsules (at 1 gram/capsule) are administered orally daily. The capsules may be administered either once daily or as 2 capsules two times daily.	Dietary Supplement: Omega-3 fatty acid Patients receive omega-3 fatty acid capsules orally beginning 1 week prior to paclitaxel treatment. Capsule administration continues until paclitaxel is discontinued or for 12 weeks maximum (whichever comes first). Each 1-gram capsule contains approximately 465 mg eicosapentaenoic acid (EPA) and 375 mg docosahexaenoic acid (DHA). Other Names: Fish oil n-3 fatty acid O3FA Lovaza Drug: Paclitaxel Patients will receive, as part of their standard of care, weekly paclitaxel at 70 to 90 mg/m2 intravenously for a minimum of 2 months. Treatment 3 out of 4 weeks is allowed. Other Names: Taxol
Placebo Comparator: Arm II (placebo) Four placebo capsules (at 1 gram microcrystalline cellulose/capsule) are administered orally daily. The capsules may be administered either once daily or as 2 capsules two times daily.	Dietary Supplement: Placebo Patients receive placebo capsules orally beginning 1 week prior to paclitaxel treatment. Capsule administration continues until paclitaxel is discontinued or for 12 weeks maximum (whichever comes first) Drug: Paclitaxel Patients will receive, as part of their standard of care, weekly paclitaxel at 70 to 90 mg/m2 intravenously for a minimum of 2 months. Treatment 3 out of 4 weeks is allowed. Other Names: Taxol

Arm

Intervention/Treatment

Experimental: Arm I (Omega-3 fatty acid)

Four Omega-3 fatty acid capsules (at 1 gram/capsule) are administered orally daily. The capsules may be administered either once daily or as 2 capsules two times daily.

Dietary Supplement: Omega-3 fatty acid

Patients receive omega-3 fatty acid capsules orally beginning 1 week prior to paclitaxel treatment. Capsule administration continues until paclitaxel is discontinued or for 12 weeks maximum (whichever comes first). Each 1-gram capsule contains approximately 465 mg eicosapentaenoic acid (EPA) and 375 mg docosahexaenoic acid (DHA).

Other Names:

Fish oil

n-3 fatty acid

O3FA

Lovaza

Drug: Paclitaxel

Patients will receive, as part of their standard of care, weekly paclitaxel at 70 to 90 mg/m2 intravenously for a minimum of 2 months. Treatment 3 out of 4 weeks is allowed.

Other Names:

Taxol

Placebo Comparator: Arm II (placebo)

Four placebo capsules (at 1 gram microcrystalline cellulose/capsule) are administered orally daily. The capsules may be administered either once daily or as 2 capsules two times daily.

Dietary Supplement: Placebo

Patients receive placebo capsules orally beginning 1 week prior to paclitaxel treatment. Capsule administration continues until paclitaxel is discontinued or for 12 weeks maximum (whichever comes first)

Drug: Paclitaxel

Patients will receive, as part of their standard of care, weekly paclitaxel at 70 to 90 mg/m2 intravenously for a minimum of 2 months. Treatment 3 out of 4 weeks is allowed.

Other Names:

Taxol

Outcome Measures

Primary Outcome Measures

Mean severity of pain [Up to 1 month after completion of therapy]
Differences between groups will analyzed via t-tests or Wilcoxon rank-sum tests as appropriate.

Secondary Outcome Measures

Incidence of pain or relief [Up to 1 month after completion of therapy]
Fisher's exact test will be used for the incidence variable with 95% confidence intervals.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients have a diagnosis of breast cancer or ovarian cancer
Patients are scheduled to receive weekly paclitaxel at 70-90 mg/m^2 for a minimum of 2 months; 3 out of 4 weeks is allowed
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
Patients must not have taken omega-3-fatty acid supplements within the past 1 month prior to registration and must agree to refrain from use of omega- 3 fatty acid supplements from sources outside the study
Patients must not be on nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin for at least 1 week prior to registration; NSAIDS or aspirin are allowed after enrollment
Patients must not have received any other analgesics (opiates and tramadol) 1 week prior to registration; analgesics (opiates and tramadol) are allowed after enrollment
Patients must have the ability to complete questionnaires by themselves or with assistance
Patients must not be on anticoagulation medication (heparin/ warfarin) within 28 days prior to registration, because of increased risk of bleeding
Concurrent treatment with carboplatin +/- bevacizumab is allowed
Concurrent treatment with human epidermal growth factor receptor (Her2 neu) targeted therapy is allowed

Exclusion Criteria:

Known allergy to omega 3 fatty acids, fish or shellfish
Pre-existing diagnosis of peripheral neuropathy
Diagnosis of fibromyalgia
Concurrent planned neutrophil colony stimulating factor therapy
Prior exposure to paclitaxel within the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico	United States	87106
2	Presbyterian Medical Group	Albuquerque	New Mexico	United States	87110