A Pilot Randomized, Placebo Controlled, Double Blind Study of Omega-3 Fatty Acids to Prevent Paclitaxel Associated Acute Pain Syndrome
Phase: NA
Conditions: Breast Cancer, Ovarian Neoplasm, Pain
Sponsor: New Mexico Cancer Research Alliance

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New Mexico Cancer Care Alliance 
University of New Mexico Cancer Center 
         
 
 
PROTOCOL 
PROTOCOL NUMBER: INST 1211 
 
A Pilot Randomized, Placebo Controlled, Double Blind Study of Omega-3 Fatty Acids to Prevent 
Paclitaxel Associated Acute Pain Syndrome 
 
Principal Investigators: 
 
Zoneddy Dayao, MD 
 
 
 
 
 
University of New Mexico Cancer Center 
 
 
 
 
 
1201 Camino de Salud NE, MSC07 4025 
 
 
 
 
 
Albuquerque, NM 87131-001 
 
 
 
 
 
(505) 272-5490  
 
 
 
 
 
FAX: (505) 272-7799 
 
 
 
 
 
zdayao@salud.unm.edu 
 
 
 
 
 
 
Debra Barton, RN, PhD, AOCN, FAAN 
 
 
 
 
 
Mayo Clinic 
 
 
 
 
 
200 First Street S.W. 
 
 
 
 
 
Rochester, MN 55905 
 
 
 
 
 
(507) 255-3812 
 
 
 
 
 
FAX (507) 538-8300 
 
 
 
 
 
barton.debra@mayo.edu 
 
 
Co-Investigator(s): 
 
 
Melanie Royce, MD 
 
 
 
 
 
University of New Mexico Cancer Center 
 
 
 
 
 
1201 Camino de Salud NE, MSC07 4025 
 
 
 
 
 
Albuquerque, NM 87131-001 
 
 
 
 
 
(505) 925-0405 
 
 
 
 
 
FAX: (505) 272-7799 
 
 
 
 
 
mroyce@salud.unm.edu 
 
Study Sites: 
 
 
 
New Mexico Cancer Care Alliance: 
 
 
 
 
 
University of New Mexico, Lovelace Health Systems,  
                                                             
Presbyterian Healthcare Services, Memorial Medical  
 
 
 
 
 
 
Center, Christus St. Vincent Regional Medical Center, 
 
 
 
 
 
Hematology-Oncology Associates, New Mexico Cancer 
                                                             
Care Associates 
 
Study Agent:  
 
 
Omega-3 Fatty Acids 
 
Funding Source(s):  
 
 
NCCTG 
 
Protocol Date:  
 
 
August 21, 2012; Version 1.0 
 
Revised Protocol Date: 
 
October 17, 2012; Version 2.0 
Revised Protocol Date:  
 
January 09, 2013;  Version 3.0 
 
  
April 1, 2016;  Version 4.0 

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New Mexico Cancer Care Alliance 
University of New Mexico Cancer Center 
         
 
 
INST 1211 
 
SIGNATURE PAGE 
 
 
The signature below constitutes the approval of this protocol and all attachments as necessary. It provides 
the necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable U.S. federal regulations and ICH guidelines. 
 
Principal Investigator (PI) Name: Zoneddy Dayao, M.D.  
 
PI Signature:  _____________________________ 
 
Date:   
_____________________________ 
 

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Background and Rationale (including feasibility) 
 
Paclitaxel, a widely used chemotherapeutic agent, is associated with several well-known side effects 
including neuropathy and generalized body aches (1).  The latter has recently been described as 
paclitaxel- associated acute pain syndrome (P-APS) and often occurs in the 1st 3-4 days after 
administration (2).  It affects about 58-90% of patients (2, 10).  Previously, these symptoms have been 
described as myalgias and arthralgias (1).  However, recent data support that P-APS may in fact be an 
early manifestation of neuropathy, as opposed to being musculoskeletal in origin. For instance, it was 
noted that patients with higher P-APS pain scores with the first dose of paclitaxel are at risk for 
developing chronic neuropathy (2, 3). 
 P-APS can be severe, and may require use of potent analgesics for symptom control.  Non-steroidal anti-
inflammatory drugs (NSAIDs) are frequently used as frontline therapy. However, there is concern over 
side effects including gastrointestinal bleeding and acute renal injury.  Many therapies have been studied 
including steroids (4), glutamine (5), antihistamine (6), opioid analgesics, and herbs (7), with variable 
results. 
Low dose oral prednisone starting 24 hours after completion of chemotherapy and continued for a total of 
5 days has been previously reported to result in substantial improvement in symptomatology (3). 
However, this study was limited due to the small sample size.  In addition, given the variable schedule of 
paclitaxel ranging from weekly to every 3 weeks, this regimen could result in a significant amount of 
prednisone and can increase the risk of side effects over time. 
In a placebo-controlled, double blind randomized crossover trial, the effect of glutamine on paclitaxel 
associated myalgias and arthralgias showed that glutamine, although well tolerated, had no effect on the 
development and severity of symptoms, as reported by the treating physician and by patient log (5).  
Oral low-dose antihistamine, in the form of terfenadine 60 mg at the onset of pain and subsequently, has 
been reported to be temporarily effective in controlling paclitaxel-induced myalgia and /or dysesthesia 
(5). However, this study was also limited by its sample size with only 9 patients included. 
Currently, there is no standard of care for P-APS.  Since paclitaxel is a commonly used chemotherapeutic 
agent and P-APS is common and can be debilitating to some patients, an agent with a favorable toxicity 
profile that may prevent P-APS and possibly prevent the development of neuropathy will have significant 
clinical utility.  
 
Data on the Pathophysiology of Paclitaxel-Associated Acute Pain Syndrome 
The mechanism of P-APS is currently unknown.  For many years, these subacute aches and pains were 
described as myalgias/ arthralgias based on patient reported symptoms.  The self-limited course led to a 
hypothesis that symptoms are possibly the result of an inflammatory reaction to paclitaxel (1,3).  More 
recently, Loprinzi et al reported the natural history of P-APS (2,3). In this study, P-APS symptoms were 
assessed in 94 patients using patients’ daily symptom log with 10 items assessing pain symptoms and 
used of pain medication, adapted from Cleeland’s Brief Pain Inventory (Appendix I).  In addition, a 22-
item summary questionnaire regarding symptom characteristics was given after paclitaxel use.  
Chemotherapy-induced peripheral neuropathy (CIPN) symptoms were assessed using the validated 
EORTC (European Organization for Research and Treatment of Cancer) Quality of Life Questionnaire 
(QLQ)-CIPN-20 given at baseline and weekly after each paclitaxel dose.   

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With regards to the P-APS, it was noted that the most common manifestation was a diffuse achiness 
mainly involving the legs, hips and lower back, typically evolving over 1-4 days.  Interestingly, in the 
weekly paclitaxel treatment group, the initial pain experienced with the first treatment did not predict the 
severity of pain with additional doses, but appeared to predict the severity of symptoms associated with 
peripheral neuropathy, predominantly sensory, which evolved over the 12-week period of treatment. This 
is the first study showing that the P-APS may in fact be an early manifestation of neuropathy and is 
associated with the development of chronic neuropathy (2, 3). 
One mechanism proposed for P-APS is an early inflammatory process characterized by macrophage 
activation in both the DRG and peripheral nerve occurring shortly after paclitaxel therapy (9).  
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 (9). Therefore, it is 
possible that paclitaxel-induced neuropathic pain may be mediated by proinflammatory cytokines. If P-
APS and chronic neuropathy are indeed part of a continuum, the inflammatory pathway would be a 
reasonable target for therapy.   
The exact mechanism on how paclitaxel eventually leads to the development of neuropathy is still not 
understood.  Taxanes promote stabilization of microtubules leading to disruption of normal cell division, 
and eventually resulting in cell death.  Results of a study showed that short-term administration of 
paclitaxel induces mainly reversible changes in the peripheral nerves and spinal roots (8). Microtubules 
seem to be the main target of paclitaxel neurotoxicity, in much the same way as has been described for its 
antineoplastic activity. It has been hypothesized that microtubule-dependent axonal transport is disrupted 
by paclitaxel. Abnormal aggregation of microtubules in neuronal cells is hypothesized to contribute to 
neurosensory abnormalities leading to impairment of axonal transport (8).  
Taken together, 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. 
 
Rationale for Studying Omega 3 Fatty Acids to Prevent or Ameliorate  P-APS 
Omega 3 Fatty Acids:  Anti-Inflammatory Properties and P-APS.  
Essential polyunsaturated fatty acids (PUFA) have two major families, the omega-6 (n-6) and omega-3 
(n-3).  The 20 carbon (n-3) and (n-6) fatty acids compete for the same enzymes and therefore, the intake 
of one omega fatty acid will diminish the metabolism of the other (10,15).   
Arachidonic Acid (AA) is a primarily diet-derived 20 carbon omega-6 PUFA which serves as a precursor 
of proinflammatory metabolites such as prostaglandins, thromboxanes and leukotrienes (10). These 
eicosanoids are involved in modulating the intensity and duration of an inflammatory response. 
Cyclooxygenase (COX) enzymes are the rate limiting enzymes in the conversion of AA to prostaglandin 
E2 (PGE2) and are a target for therapy, of which the most widely studied are the NSAIDS. 
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 (10, 11).  
EPA competes with AA for enzymatic metabolism, thereby decreasing inflammatory derivatives.   
Recently, omega-3 PUFAs have also been identified as precursors of anti-inflammatory mediators called 
protectins and resolvins.  Resolvins occur in the resolution phase of inflammation.  Protectin D1 was 

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initially found to decrease damage of brain ischemia-reperfusion injury and thus named neuroprotectin 
D1 (12-14). 
Several clinical studies have reported the pain relieving effects of omega 3 fatty acids for inflammatory 
joint diseases.  In a recent meta-analysis of 17 trials, supplementation of omega-3 fatty acids for 3-4 
months resulted in reduction in patient reported pain severity, duration of morning stiffness and amount 
of NSAID consumption (11).  
As noted above, there is evidence that early inflammatory processes are observed in paclitaxel induced 
nerve damage. This may in part account for the symptoms of P-APS, and sustained inflammation may 
lead to downstream effects responsible for evolution of peripheral neuropathy (8, 9).  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 (12-14).  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. 
 
Omega 3 Fatty Acids:  A Dietary Supplement with Neuroprotective Properties 
The nervous system is richly endowed with omega-3 fatty acids, primarily DHA.  Omega-3 fatty acids may 
act as natural neuroprotective agents, as well as key components in nerve hemostasis.  Several studies have 
reported the role of omega-3 fatty acids in maintaining nerve integrity and function (16, 21). Long chain n-
3 PUFAs such as docosahexaenoic acid (DHA) have been shown to have promising in the treatment of a 
broad range of neurodegenerative conditions (16).   
Several preclinical models have shown the neuroprotective effect of DHA in models of spinal cord injury 
(17- 19).  A mouse model has recently been used comparing groups with different fatty acid profiles (19).  
One group expressed the fat-1 gene from Caenorhabditis elegans, which encodes a fatty acid desaturase, 
the enzyme that converts n-6 into n-3 PUFAs, leading to enrichment in tissue n-3 PUFA levels (low n-6/n-
3 ratio). This was compared to the group that had a high n-6/ n-3 ratio as well as to wild type strain.  Utilizing 
in vitro and in vivo injury models, neurite growth, axonal regeneration, sensory and motor function were 
assessed and compared. Interestingly, the dorsal root ganglion neurons from fat-1 mice ( n-3 enriched) had 
significant increase in neurite outgrowth and improved neuronal survival after injury. The omega-3 
enriched group did not exhibit an increase in neuronal cell death after mechanical or hypoxic injury, in 
contrast to the 2 groups where hypoxia resulted in neuronal cell death in the order of 2.3 - 2.6 fold increase. 
The mice expressing the fat-1 gene showed a more complex neurite outgrowth phenotype, with neurons 
displaying both longer neurites and branches, supporting the notion that n-3 PUFA level had improved 
neuroregenerative potential. Interestingly, the in vivo experiments also showed that the higher tissue n-3 
PUFA group also exhibited a faster recovery of sensory loss, as assessed by mechanical stimulation 
thresholds.  Even after a severe form of injury such as a crush injury, recovery of sensation was faster in 
the group that was enriched for omega-3.   
In the clinical setting, omega-3 fatty acids have been studied in a wide spectrum of neurodegenerative 
disorders (21- 24).  Alzheimer’s disease, a progressive neurodegenerative disease, has been reported to 
strongly correlate with decreases in omega -3 fatty acid levels in the brain and peripheral tissue compared 
to age-related controls (22).  Epidemiological studies have also shown a correlation between lower levels 
of dietary omega-3 fatty acids and the development of Alzheimer’s disease (23), suggesting a 

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neuroprotective effect.  Similar observations have been seen in Parkinson’s disease, a neurodegenerative 
disorder of the basal ganglia (24).  Dietary interventions however have shown conflicting results. 
There are also emerging data on the role of omega-3 fatty acid supplementation in acute neurologic injuries. 
As an example, it was reported that administration of moderate to high dose human albumin rich in DHA 
is neuroprotective in focal brain ischemia (25).   
These observations lend credence to the notion that omega-3 fatty acids promote neuroprotection and 
neuroregeneration.  These, along with its anti-inflammatory properties make it an attractive agent to study 
in the prevention and amelioration of paclitaxel induced peripheral neuropathy. We hypothesize that 
omega-3 fatty acid supplementation started prior to initiation and administration of chemotherapy can 
potentially attenuate paclitaxel induced nerve damage.  
 
Omega 3 Fatty Acids and Paclitaxel 
Currently, there are no documented safety concerns with the combination of omega-3 fatty acids and 
paclitaxel.  On the contrary, preclinical and clinical studies have investigated the potential synergy with the 
combination treatment (26-28).  In early preclinical data, sequential exposure to Omega-3 PUFA 
docosahexanoic acid (DHA) followed by paclitaxel or docetaxel was demonstrated to enhance cytotoxicity 
of taxanes against the metastatic breast cancer cell line MDA-MB-231 (26). The investigational drug 
Taxoprexin  (DHA-Paclitaxel), a 2’-O-acyl conjugate of paclitaxel covalently bound to DHA via an ester 
bond, was developed to improve paclitaxel’s therapeutic performance.  Phase I trials did not show any dose 
limiting toxicities with the conjugated preparation (27).  Oral omega-3 fatty acids, classified as a nutritional 
additive, have several commercial preparations available for over the counter use. To date, there are no 
reported adverse drug reactions with FDA approved Lovaza and paclitaxel. 
 
Feasibility 
P-APS is common and occurs in about 50-90% of patients.  Paclitaxel is a common chemotherapeutic 
agent used in a variety of malignancies, both in the early and advanced setting.  Therefore, it is expected 
that the many patients will be eligible for this clinical trial. 
Omega-3 fatty acids have a well-established safety profile and have led to their wide availability and over 
the counter use. As detailed above, its anti-inflammatory properties and favorable side effect profile make 
them an attractive alternative to NSAIDS.  Furthermore, its potential neuroprotective properties make 
them an intriguing candidate for testing in paclitaxel induced neuropathy. 
This will be a multi-institutional study and the Principal Investigators are Zoneddy Dayao, MD (NCCTG) 
from the University of New Mexico Cancer Center and Debra Barton, RN, PhD (NCCTG)  from the 
Mayo Clinic, Rochester, MN.  Melanie Royce, MD, PhD (ACOSOG) from the University of New 
Mexico is a co-investigator. The primary site will be the New Mexico Cancer Care Alliance (NMCCA), 
as defined below.  
New Mexico Cancer Care Alliance is a New Mexico nonprofit corporation established in February, 2002, 
that functions as a single point of contact for the management of oncology trials at multiple sites. 
NMCCA  includes: University of New Mexico Cancer Research and Treatment Center; Lovelace Health 
Systems; the New Mexico Veterans Affairs Health Care System; Presbyterian Healthcare Services 
(Presbyterian Hospital, Presbyterian Kaseman Hospital, Presbyterian Medical Group); Memorial Medical 
Center, Christus St. Vincent Regional Medical Center; Hematology-Oncology Associates; New Mexico 

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Cancer Care Associates and  New Mexico Ear, Nose, Throat Specialists, P.C.; PMG Surgery. It is a joint 
venture representing approximately 100 physicians in central, northern and southern New Mexico who 
are engaged in the care of cancer patients.  
The NMCCA utilizes a centralized IRB for all participating sites: either the University of New Mexico 
Human Research Review Committee (HRRC), or the Western IRB.  Each trial has only one full review 
regardless of how many sites will participate. 
NMCCA has a strong commitment to clinical trial accruals. From 2010-2011, a total of 517 patients were 
enrolled in therapeutic and cancer control trials, with 229 from UNM and 288 from the other sites.  The 
last 5 years have shown a steady increase in clinical trial enrollment, with  a total of 2214 patients accrued 
at all sites from 2006-2011. 
 
B. Aims 
Primary  
1. To determine whether omega-3 fatty acids can prevent or ameliorate paclitaxel associated pain 
syndrome (P-APS) in cancer patients. 
Secondary  
1. To determine whether omega-3 fatty acids can prevent development of peripheral neuropathy. 
2. To assess tolerability of omega-3 fatty acids in this setting. 
3. To compare QOL with omega-3 fatty acids supplementation versus placebo.  
 
C. Study Plan 
Eligibility criteria: 
1. Patients have a diagnosis of breast cancer or ovarian cancer. 
2. Patients must be ≥ 18 years old 
3. Patients may be either male or female 
4. Patients are scheduled to receive weekly paclitaxel at 70-90 mg/m2 for a minimum of 2 months. 3 
out of 4 weeks is allowed. 
5. ECOG Performance Status (PS) of 0, 1 or 2 
6. 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. 
7. Patients must not be on NSAIDS or aspirin for at least 1 week prior to registration. NSAIDS or 
aspirin are allowed after enrollment. 
8. Patients must not have received any other analgesics (opiates and tramadol) 1 week prior to 
registration. Analgesics (opiates and tramadol) are allowed after enrollment. 
9. Patients must have the ability to complete questionnaires by themselves or with assistance. 

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10. Patients must not be on anticoagulation medication (heparin/warfarin) within 28 days prior to 
registration, because of increased risk of bleeding.  
11. Concurrent treatment with carboplatin +/- bevacizumab is allowed. 
12. Concurrent treatment with Her2 neu targeted therapy is allowed.  
 
Exclusion Criteria 
1. Known allergy to omega-3 fatty acids, fish, or shellfish 
2. Pre-existing diagnosis of peripheral neuropathy 
3. Diagnosis of fibromyalgia 
4. Concurrent planned neutrophil colony stimulating factor therapy 
5. Prior exposure to paclitaxel within the last 6 months 
 
Protocol Treatment: 
Treatment:  Omega-3 Fatty Acid: 4 capsules (1 gram/capsule) or a double-blinded placebo either once 
daily or 2 capsules two times daily beginning 1 week prior to starting paclitaxel and continued until 12 
weeks or until paclitaxel is discontinued, whichever comes first (maximum of 12 weeks).  
Rationale for dosing:  A dose of at least 2.7 g/day of EPA and DHA have been reported to have 
analgesic effects in inflammatory conditions (11). 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. 
Formulation of omega-3-fatty acid:  Lovaza (omega-3-acid ethyl esters) capsules will be used.  Each 1-
gram capsule of Lovaza contains approximately 465 mg EPA and 375 mg DHA.  
Formulation of placebo:  Placebo will be provided by Clinical Encapsulation Services or UNM 
Pharmacy.  Excipient material will be microcrystalline cellulose. It will be odorless like Lovaza. Since the 
placebo may slightly differ from Lovaza, the pills will be dispensed in opaque bottles and providers will 
not be allowed to open them.  In addition, to document blinding, the patients will be asked on cycle 1 Day 
2, if they know what medication they are receiving.  
Randomization:  Clinical Encapsulation Services or UNM Pharmacy will package both placebo and 
active drugs.  Our pharmacy will take care of randomization.  Then our research nurses will dispense the 
drug. 
 
Measurement tools:   
For P-APS symptoms, there will be 4 types of questionnaires, adapted from NCCTG N08C1: (1) a 
baseline/pretreatment questionnaire.  (2) a daily paclitaxel induced acute pain syndrome symptom log from 
Day 2-7 (2, 20).  (3) day 8 P-APS symptom summary.  (4) 1 month after completion of paclitaxel 
questionnaire. 

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For chemotherapy-induced peripheral neuropathy (CIPN) neurotoxicity, the EORTC-QLQ CIPN20 
patient questionnaire will be used.  The questionnaire will be filled out on the 8th day of each chemotherapy 
treatment and 1 month after completion of therapy.  
Dietary counseling:  As omega-3 fatty acid metabolism is affected negatively by the amount of arachidonic 
acid in the diet, dietary counseling will be provided to assess the fatty acid intake.  Omega-3 and Omega-6 
Fatty Acid Dietary Intake Questionnaire will be given at baseline, Week 2, Week 4 and monthly thereafter 
(prepared by Laura Taber, PhD). 
Laboratory tests:  Due to a small risk of increased LDL and transaminase levels, LDL and transaminase 
levels will be determined at baseline, at Week 4 and the last day of paclitaxel treatment. 
 
D. Adverse Events 
Adverse events (AEs) will be assessed according to the National Cancer Institute’s Common Toxicity 
Criteria for Adverse Events (NCI-CTCAE) version 4.0.  Adverse events will be assessed to determine 
tolerability as part of the secondary objectives of the study.  Analyses will be performed for all patients 
having received at least one dose of omega-3 (Lovaza).  Recording of AEs and their attribution (whether 
they are due to omega-3 or due to standard of care chemotherapy treatment (paclitaxel) is important to 
determining the tolerability of omega-3.  Since this study focuses on determining whether omega-3 can 
prevent P-APS and/or peripheral neuropathy as well as the tolerability of omega-3 in patients undergoing 
treatment with paclitaxel, the scope of AE collection will be limited to: 
1) Any AEs involving aches or pain 
2) Any AEs involving neuropathy 
3) Any AEs that are definitely, probably, or possibly related to omega-3/placebo or paclitaxel 
In addition to recording AEs, data will be captured on whether AEs attributed to omega-3 or AEs 
involving aches, pains, or neuropathy cause a given patient to discontinue participation in the study. 
Reported adverse reactions for omega-3 fatty acids are minimal.  While none of these symptoms require 
dose modification or discontinuation for safety concerns, patients may discontinue therapy should they 
choose, or if they are experiencing significant discomfort.  The common side effects reported in at least 
3% or greater rate than placebo in prior clinical trials using Lovaza are as follows: 
(1) Eructation (belching) which occurs in about 4%  
(2) Dyspepsia occurring in about 3%  
(3) Altered taste in about 4% 
(4) As Lovaza contains omega-3 fatty acids obtained from several fish sources, patients with known 
hypersensitivity or allergy to fish/shellfish are excluded. However, a person who develops a rash on the 
1st week of Lovaza treatment, prior to paclitaxel administration, should be evaluated for Lovaza allergy. 
The rash should be graded per NCI-CTAE version 4 criteria and be recorded as a possible Lovaza allergy. 
 
Paclitaxel Side Effects:   These should be reported per NCI-CTAE version 4.  Dose modification of 
paclitaxel will be at the discretion of the treating physician. 
Side effects of paclitaxel include:  

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1) neutropenia,  
2) transaminitis,  
3) neuropathy,  
4) hypersensitivity reactions,  
5) alopecia,  
6) arthralgias  
7) myalgias.  
Patients who discontinue paclitaxel treatment due to allergy to paclitaxel will not be evaluable. 
 
E. Data Analysis 
In this pilot study, the effect of omega-3 on severity of paclitaxel associated pain syndrome will be evaluated 
in 60 patients using 1:1 randomization into omega-3 plus paclitaxel group and placebo plus paclitaxel group 
to achieve the primary aim. The primary endpoint will be determined by questions in N08C1 pain inventory.  
Mean severity will be calculated for each group and differences between groups will analyzed via t-tests or 
Wilcoxon rank-sum tests as appropriate.  We will also consider a binary variable for incidence (no pain 
versus any pain, no relief versus any relief, does not interfere versus other) to evaluate the primary aim.  A 
formal sample size justification based on statistical hypothesis is not applicable to this pilot study. 
Considering 60%-80% incidence of paclitaxel associated pain syndrome, we can detect a minimal 
difference of 37.6%-37.9% pain syndrome difference base on 5% significance level and 80% power with 
our proposed sample size. In this effect size calculation, the significance level actually achieved by this 
design is 2.2%-2.6%. Our sample size justification is based on primary aim with a binary variable of 
incidence. 
Similarly, we will consider both continuous variables and binary incidence variable for the secondary aims.  
For continuous variables, t-tests or Wilcoxon rank-sum tests will be used. Fisher’s exact test will be used 
for the incidence variable with 95% confidence intervals. 
Patients will be evaluable regardless of the number of cycles of paclitaxel completed.  A patient will be 
considered evaluable if they have completed a baseline pre-paclitaxel questionnaire and at least one 
questionnaire during paclitaxel treatment. 
The study will last for approximately 5 years including data analysis. 
 
F. Data Safety Monitoring: 
Data Safety Monitoring will be done by the University of New Mexico Data Safety Monitoring Board. 
 
G.  Budget:  See attached 
 
H. References 
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20. Cleeland C: How to assess cancer pain, in Tuck DC, Medzak R (eds):  Handbook of Pain 
Assessment. New York, NY.  The Guilford Press, pp 360-387, 1992 
21. Dyall, SC., Michael-Titus AT. Neurological Benefits of Omega-3 Fatty Acids.  Neuromol Med 
10:219- 235, 2008 
22. Kyle, DJ, Schaefer, E., Patton, G.,Beiser, A. Low serum docosahexaenoic acid is a significant 
risk factor for Alzhemier’s dementia.  Lipids, 34 (Suppl) S245, 1999 
23. Barberger-Gateau, P., Letenneur, L., Deschamps, V. Peres, K. Dartigues, JF, Renaud S.  Fish, 
meat and risk of dementia: Cohort study. British Medical Journal, 325, 932-933, 2002 
24. De Lau, LM, Bornebroek, M. Witteman, JC., Hofman, A. Koudstaal, PJ, Breteler MM. Dietary 
fatty acids and the risk of Parkinson disease:  The Rotterdam study, Neurology, 64 (12), 2040-
2045, 2005                                                          
25. Belyev, L, Liu Y. Zhao W, Busto R, Ginsberg, MD Human albumin therapy of acute ischemic 
stroke:  Marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. 
Stroke 32(2), 553-560, 2001  
26. Menendez JA, Lupu R, Colomer R. Exogenous supplementation with omega -3 polyunstaurated 
fatty acid docosahexanoic acid ( DHA; 22: 6n3) synergistically enhances taxane cytotoxicity and 
downregulates Her2/neu (c-erbB-2) oncogene expression in human breast cancer cells: Eur J 
Cancer Prev Jun;14 (3) 263-70, 2005 
27. Fracasso PM, Picus J, Wildi JD, Goodner SA, Creekmore AN, Gao F, Govindan R, Ellis MJ, Tan 
BR, Linette GP, Fu CJ, Pentikis HS, Zumbrun SC, Egorin MJ, Bellet RE.  Phase 1 and 
Pharmacokinetic study of weekly docosahexanoic acid-paclitaxel Taxoprexin, in resistant solid 
tumor malignancies: Cancer Chemother Pharmacol, Feb;63(3); 451-8, 2009 
 

. 
 
14 
TEST SCHEDULE 
 
 
 
Test and Procedures 
 
Baseline 
(Baseline or <28 
days after 
registration) 
Daily, Days 2-7 
following each 
paclitaxel dose 
Day 8 following 
each paclitaxel 
dose 
1 Month after 
completion of  
Therapy 
Baseline Pre-
Paclitaxel 
Questionnaire 
(Appendix 1) 
 
X 
 
 
 
Toxicity (AE) 
Assessment 
X 
 
X  
(+/- 3 days) 
X 
Daily Paclitaxel- 
Induced acute pain 
Syndrome Symptom 
Log (Appendix II) 
 
 
 
X 
**On Day 2 of cycle 1 
only, patients will 
answer question #11 
 
 
Day 8 PAPS Symptom 
Summary 
Questionnaire 
(Appendix III) 
 
 
 
X 
 
EORTC QLQ-CIPN20 
Questionnaire 
(Appendix IV) 
 
 
 
X 
 
X 
1 Month post 
paclitaxel 
Questionnaire 
(Appendix V) 
 
 
 
 
X 
Dietary Counseling 
X 
 
 
 
Dietary Questionnaire 
(Appendix VI) 
 
 
Week 2 and Week 4, 
then monthly 
thereafter 
X 
Lipid panel 
X 
 
Week 4 
X 
LFTs 
X 
 
Week 3 or 4 
 

. 
 
15 
APPENDIX  I 
Baseline Pre-paclitaxel Questionnaire 
Patient Study ID Number: _________________________ 
Date:_______________________ 
Directions:  Please answer the following questions:  
1. 
Do you have any chronic aches and pains? (Circle Yes or No) 
 
Yes 
 
 
No 
2. 
Do you regularly take pain medications? (Circle Yes or No)  
              Yes 
 
 
No (If no, go to question 4) 
3.    If yes, please list the name of each medication:    
 
 
________________________________________ 
 
________________________________________ 
4  
How much of a problem was numbness and/or tingling in your hands or fingers over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
numbness or 
tingling  
 
 
 
 
 
 
 
 
 
Numbness/tingling 
as bad as it can be 
5    How much of a problem was numbness and/or tingling in your feet or toes over the last week  (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No numbness 
or tingling  
 
 
 
 
 
 
 
 
 
Numbness or 
tingling as 
bad as it can 
be 
  6.   How much of a problem was burning or shooting PAIN in your hands and fingers over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No pain   
 
 
 
 
 
 
 
 
 
Pain as bad as 
it can be 
 
     7.     How much of a problem was burning or shooting PAIN in your feet or toes over the last week   (circle one number)?  
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No pain   
 
 
 
 
 
 
 
 
 
Pain as bad as 
it can be 
 
 
 
 

. 
 
16 
Appendix II 
Daily Paclitaxel- Induced Acute Pain Syndrome Symptom Log 
Patient Study ID Number: _________________________ 
Day# _________  Date:__________ 
 
1. 
Please rate any aches/pains that are NEW since your last dose of paclitaxel, and that you think might be related to your 
chemotherapy treatment by circling ONE number that best describes your aches/pains at its WORST in the last 24 
hours. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
 
 
 
 
 
 
 
 
        Aches/pains as bad  
pain 
 
 
 
 
 
 
 
 
         as can be 
 
 
2. 
Please rate the same aches/pains by circling the ONE number that best describes your pain at its LEAST in the last 24 
hours. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
 
 
 
 
 
 
 
 
        Aches/pains as bad  
pain 
 
 
 
 
 
 
 
 
         as can be 
 
3. 
Please rate the same aches/pain by circling the ONE number that best describes your aches/pains on the AVERAGE in 
the last 24 hours. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
 
 
 
 
 
 
 
                   Aches/pains as bad  
pain 
 
 
 
 
 
 
 
 
      as can be 
 
4. 
 Have you used nonprescription medication, like aspirin , Tylenol, Motrin, Ibuprofen or Advil, for the pain in the last 
24 hours ( Circle Yes or No) 
 
Yes                         No  ( If no, go to question 7) 
 
 
5. 
 If yes, please list the name of each medications 
 
____________________________                           _______________________________ 
____________________________                           _______________________________ 
 
 
 

. 
 
17 
6. 
If yes, please rate by circling ONE number how helpful these nonprescription medications were in controlling your 
pain in the last 24 hours. 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
 
 
 
 
 
 
 
 
        Aches/pains as bad pain 
 
 
 
 
 
 
 
 
        
 
        as can be 
 
                                                                               
7. 
Have you used opioid medications like codeine, oxycodone or morphine for this pain in the last 24 hours ( Circle Yes 
or No)  
  
Yes                  No (If no, go to question 10) 
 
 
8. 
 If yes, please list the name of each medication: 
 
______________________                                _______________________________ 
                 ______________________                                _______________________________ 
 
9. 
 If yes, please rate by circling ONE number how helpful these opioid pain medications were in controlling your pain in 
the last 24 HOURS. 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Not helpful,                                                                                                      Completely helpful 
             No pain control 
 
 
 
 
 
 
          No pain after taking drug 
 
 
 
 
 
 
 
 
 
 
 
10.  Other comments: 
 
________________________________________________________________________________________________
________________________________________________________________________________________________ 
 
 
 
11.     Day 2 Cycle 1 only: 
                What drug do you think you are taking?     Placebo             Lovaza          I don’t know/ I can’t tell 
 
 
 
 
 
 
 
 
 

. 
 
18 
 
APPENDIX III 
Day #8 Paclitaxel-induced Acute Pain Syndrome Symptom Summary 
Patient Study ID Number: _________________________ 
Date:________________ 
Directions:  Please answer the following questions:  
1. 
Over the previous week, have you developed any NEW aches/pains that you did not have prior to your last dose of chemotherapy and 
that you think is from this chemotherapy? 
 
Yes 
 
 
No 
 
 
If NO, then you can skip to question 18. 
2. 
Please rate any aches/pains that you have by circling ONE number that best describes your aches/pains at its worst over the last week. 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No aches or 
pains   
 
 
 
 
 
 
 
 
 
Aches or 
pains  as bad 
as  can be 
3.   Please place a CHECK mark (√) by all of the appropriate words that could be used to describe this  
pain? 
 
 _____Sharp 
          _____Dull 
 
 
 
_____Throbbing 
 
_____Cramping 
 
_____Stabbing 
 
  
 
_____Gnawing 
 
 
_____Burning-hot 
 
_____Aching 
 
_____Heavy 
 
 
_____Splitting 
 
 
_____Shooting 
 
 
_____Stinging 
 
 
_____Pulsating 
 
 
 
 
 

. 
 
19 
4.  
Please place a CHECK mark (√) by the two words that are most descriptive of your pain:   
 
_____Sharp 
 
_____Dull 
 
 
 
_____Throbbing 
 
_____Cramping 
 
_____Stabbing 
 
  
 
_____Gnawing 
 
 
_____Burning-hot 
 
_____Aching 
 
_____Heavy 
 
 
_____Splitting 
 
 
_____Shooting 
 
 
_____Stinging 
 
 
_____Pulsating  
  
5.   Please list any other words that might describe these aches/pains 
_____________________________________________________________________________________________________________________
_____________________________________________________________________________________________________________________
__________________________________________________________________________________________________________ 
 
 
6. 
Please indicate where these NEW pains are/were located by placing a CHECK mark (√) next to the  
location(s), please mark all that 
apply: 
_____Arms, above the elbow 
_____Arms, between the elbows and wrists  
_____Hands  
_____Legs above knee 
_____Legs, between the knee and ankles 
_____Feet 
_____Upper back 
_____Lower back 
_____Neck 
_____Head  
_____Chest  

. 
 
20 
_____Abdomen 
_____Hips  
_____Shoulders  
_____Other, please specify  ____________________________________________________ 
 
7.  
Please note whether walking or standing increased any new pain that you had after the paclitaxel you  received (Circle one number)                                                    
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not at all    
 
 
 
 
 
 
 
 
 
Yes, quite a 
bit  
8. 
Please note whether light touching of areas of pain increased any new pain that you had after the paclitaxel you received. (Circle one 
number) 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not at all    
 
 
 
 
 
 
 
 
 
Yes, quite a 
bit  
 
9. 
Have you used nonprescription medications, like aspirin, Tylenol, Motrin, ibuprofen or Advil, for this pain over the last week? (Circle yes 
or no)  
 
Yes 
 
 
No (If no, go to question 12) 
10.  If yes, please list each medication and estimate how many you took of each over the past week: 
 
 
Medication: 
 
 
 
 
Number used over the past week:  
 
 
___________________________ 
___________________________ 
 
 
___________________________ 
___________________________  
 
 
 
11.    If yes, please rate by circling ONE number how helpful these nonprescription medications were in controlling your pain overall during the 
last week.     
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not helpful, 
no pain 
control    
 
 
 
 
 
 
 
 
 
Extremely 
helpful, no 
pain after 
taking the 
drug(s) 
 
12       Have you used opioid pain medications (e.g. codeine, oxycodone, morphine, etc) for this pain over the last week? (Circle Yes or No) 
 
Yes 
 
 
No (If no, go to question 15) 
 
 
 

. 
 
21 
13. If yes, please list each medication and estimate how many you took of each over the past week: 
 
 
 
                    Medication: 
 
                  Number used over the past week:  
 
 
___________________________ 
___________________________ 
 
 
___________________________ 
___________________________ 
 
                                                                                                                              
14.  If yes, please rate by circling ONE number how helpful these opioid pain medications were in controlling your pain overall during the last 
week.   
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not helpful, 
no pain 
control    
 
 
 
 
 
 
 
 
 
Extremely 
helpful, no 
pain after 
taking the 
drug(s) 
 
15      Have you used anything else (e.g. massage, whirlpool, stretching, etc) for this pain over the last week? (Circle Yes or No) 
 
Yes 
 
 
No 
16.   If yes, please specify: ___________________________________________________ 
 
17.  If yes, please rate by circling ONE number how helpful these things were in controlling your pain overall during the last week.   
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not helpful, 
no pain 
control    
 
 
 
 
 
 
 
 
 
Extremely 
helpful, no pain 
after taking the 
treatment (s) 
 
 
18.  How much of a problem was numbness and/or tingling in your hands or fingers over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No numbness 
or tingling     
 
 
 
 
 
 
 
 
 
Numbness or 
tingling as 
bad as it can 
be  
 

. 
 
22 
 
 
 
 
 
 
 
 
 
 
 
19.  How much of a problem was numbness and/or tingling in your feet or toes over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No numbness 
or tingling     
 
 
 
 
 
 
 
 
 
Numbness or 
tingling as 
bad as it can 
be  
 
 
20.  How much of a problem was burning or shooting PAIN in your hands or fingers over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No pain     
 
 
 
 
 
 
 
 
 
Pain as bad as 
it can be  
 
21.  How much of a problem was burning or shooting PAIN in your feet or toes over the last week  (circle one number)? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No pain     
 
 
 
 
 
 
 
 
 
Pain as bad as 
it can be  
 
22.  
Other comments: 
 
_____________________________________________________________________________________ 
 
_________________________________________________________________________________ 
                                                                       

. 
 
21 
APPENDIX IV 
EORTC QLQ- CIPN20 
Patient Study ID Number: _________________________ 
Date:_____________________ 
During the past week:                                                       Not at all             A little                Quite a Bit                Very much                                                     
1. Did you have tingling fingers or hands?                                          1                            2                                 3                                    4 
2. Did you have tingling toes and feet?                                               1                            2                                 3                                    4 
3. Did you have numbness in your fingers/ hands?                          1                             2                                 3                                    4 
4. Did you numbness in your toes or feet?                                         1                             2                                 3                                    4 
5. Did you have shooting or burning pain in your fingers/               1                            2                                 3                                     4  
hands? 
6. Did you shooting or burning pain in your toes and feet?             1                            2                                 3                                    4 
7.  Did you have cramps in your hands?                                               1                            2                                 3                                    4 
8.  Did you have cramps in your feet?                                                   1                            2                                 3                                    4 
9.   Did you have problems standing or walking because                  1                            2                                 3                                    4                                          
of a difficulty feeling the ground under your feet? 
10. Did you have difficulty distinguishing between hot and cold      1                            2                                 3                                    4                                        
water? 
11. Did you have a problem holding a pen, which made writing       1                            2                                 3                                    4                                       
difficult? 
12. Did you have difficulty manipulating small objects with               1                            2                                 3                                    4                                        
your fingers (for example, fastening small buttons)? 
13.  Did you have difficulty opening a jar or bottle because               1                            2                                 3                                    4                                      
of weakness in your hands? 
14. Did you difficulty walking because your feet dropped                   1                            2                                 3                                    4                                     
downwards? 
15.  Did you have difficulty climbing stairs or getting up out              1                            2                                 3                                    4                                      
of a chair because of weakness in your legs? 
16.   Were you dizzy when standing up from a sitting or                     1                            2                                 3                                    4                                     
lying position? 
17. Did you have blurred vision?                                                               1                            2                                 3                                    4 
18.  Did you have difficulty hearing?                                                        1                            2                                 3                                     4 
19.  If you drive a car, did you have difficulty using pedals?                 1                            2                                 3                                    4 
20.  (Answer only if you are a man) Did you have                           1                            2                                 3                                    4         
difficulty getting or maintaining an erection?       

. 
                                                                                                                                                                                                                    
22 
 
Appendix V 
 
Monthly Questionnaire after paclitaxel chemotherapy completion  
Patient Study ID Number: _________________________ 
Date: _________________________________ 
 
1.   How much of a problem was numbness and/or tingling in your hands or fingers over the last week  (circle one 
number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
numbness 
or 
tingling     
 
 
 
 
 
 
 
 
 
Numbness 
or tingling 
as bad as 
it can be  
 
2.   How much of a problem was numbness and/or tingling in your feet or toes over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
numbness 
or 
tingling     
 
 
 
 
 
 
 
 
 
Numbness 
or tingling 
as bad as 
it can be  
 
3.   How much of a problem was burning or shooting PAIN in your hands or fingers over the last week (circle one 
number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No pain       
 
 
 
 
 
 
 
 
Pain as 
bad as it 
can be  
4.   How much of a problem was burning or shooting PAIN in your feet or toes over the last week (circle one number)? 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No pain      
 
 
 
 
 
 
 
 
Pain as 
bad as it 
can be  
 
6. Other Comments: 
 

. 
                                                                                                                                                                                                                    
23 
APPENDIX VI 
OMEGA-3 and OMEGA-6 FATTY ACID DIETARY INTAKE QUESTIONNAIRE 
Patient Study ID Number: _________________________ 
Date:__________________________________ 
 
Instructions:  You will be asked to complete this form at the time of registration, and every two weeks for the first month of the study.  
After that, you will be asked to complete this form at the completion of the study. 
By selecting one (1) box per line, please indicate your average use, during the past 2 weeks, of each specific food.  Please select a box 
by marking an “X” in it for one serving, or two or more “X ‘s” for more than one serving. 
3 oz = the size of a deck of cards 
 
 
Food 
Never or 
less than 
once per 
week 
1 
per  
week  
2  
per 
week 
3 
per 
week 
4 
per 
week 
5 
per 
week 
6 
per 
week 
7 per 
week 
(every 
day) 
2 
per 
day 
3+  
per 
day 
Whole egg 
 
 
 
 
 
 
 
 
 
 
Canned tuna fish 
 (3 oz) 
 
 
 
 
 
 
 
 
 
 
Dark meat fish (i.e. 
salmon, mackerel, 
sardines, swordfish)  
(3 oz) 
 
 
 
 
 
 
 
 
 
 
 
 
White fish (3 oz) 
 
 
 
 
 
 
 
 
 
 
Shrimp or lobster (3 
oz) 
 
 
 
 
 
 
 
 
 
 
Scallops  (3 oz) 
 
 
 
 
 
 
 
 
 
 
Chicken – white meat  
(3 oz) 
 
 
 
 
 
 
 
 
 
 
Chicken – dark meat  
(3 oz) 
 
 
 
 
 
 
 
 
 
 
Turkey – white meat  
(3 oz) 
 
 
 
 
 
 
 
 
 
 
Turkey – dark meat  (3 
oz) 
 
 
 
 
 
 
 
 
 
 

. 
                                                                                                                                                                                                                    
24 
Beef (hamburger, ribs 
or steak) 
(3 oz) 
 
 
 
 
 
 
 
 
 
 
Pork (pork chop, ribs, 
ham or roast) 
(3 oz) 
 
 
 
 
 
 
 
 
 
 
Pork or beef chile or 
stew (1/2 cup) 
 
 
 
 
 
 
 
 
 
 
Chicken or pork 
posole (1/2 cup) 
 
 
 
 
 
 
 
 
 
 
Chicken or beef taco 
or burrito 
(1 medium) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

. 
                                                                                                                                                                                                                    
25 
                                                                                   APPENDIX VII 
 
Dietary Information 
Part of this study is to collect information regarding your diet since there are certain foods rich in arachidonic Acid that 
can lower the effects of omega-3 fatty acids. 
Arachidonic Acid (omega-6) rich foods  
 
EPA and DHA (omega-3) rich foods 
Egg yolks 
 
 
 
 
 
Fish 
Chicken 
 
 
 
 
 
Shellfish 
Turkey 
Beef 
Pork 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

. 
                                                                                                                                                                                                                    
26 
APPENDIX VIII 
INST 1211 Questionnaire Summary Checklist: 
Patient Name:  
______________________________ 
Patient Study ID #: 
_________________________ 
Date Range:    
_____________ to ________________ 
This form is a checklist for use by the research coordinator.  Please use this form at visits during which questionnaires are 
collected.  After obtaining the patient’s signature, please file this form in the patient’s chart. 
 
Questionnaires: 
Baseline Pre-paclitaxel Questionnaire 
 
 
 
 
 Yes  
No 
 
N/A 
Daily Paclitaxel Induced Pain Syndrome Symptom Log  
 
 Yes  
No 
 
N/A 
Days 2 through 7 of Cycle _______ 
Day 8 Paclitaxel-Induced Acute Pain Syndrome Symptom Summary 
 Yes  
No 
 
N/A 
EORTC QLQ-CIPN20 
 
 
 
 
 
 
 Yes  
No 
 
N/A 
Monthly Questionnaire after Paclitaxel Chemotherapy Completion 
 Yes  
No 
 
N/A 
Omega-3 and Omega-6 Fatty Acid Dietary Intake 
 
 
 Yes  
No 
 
N/A 
 
I have completed the above documents as indicated above and have returned them to the clinic on the date below. 
 
________________________  
 
 
 
____________________ 
Patient Signature 
 
 
 
 
 
 
Date 
 
________________________  
 
 
 
____________________ 
Study Team Member Signature  
 
 
 
 
Date 
 

. 
                                                                                                                                                                                                                    
27 
How this pilot study will lead to an ALLIANCE protocol 
This pilot study will explore the role of omega 3 fatty acids in preventing or ameliorating the severity of paclitaxel 
associated acute pain syndrome (P-APS) and development of peripheral neuropathy in cancer patients.  This will be a 
multi-institutional study conducted by the University of New Mexico under the auspices of the New Mexico Cancer Care 
Alliance (NMCCA), a nonprofit corporation with approximately 100 physicians in central, northern and southern New 
Mexico. The NMCCA functions as a single point of contact for clinical trials.  Through this organization, cooperative trials 
including NCCTG, ACOSOG and CALGB, have been opened and several patients have been accrued. 
This feasibility trial will provide an opportunity for three investigators from the legacy groups to collaborate:  Zoneddy 
Dayao, MD (NCCTG) , Debra Barton, RN, PhD (NCCTG) and Melanie Royce, MD, PhD ( ACOSOG). This also provides an 
opportunity for mentoring a junior faculty in the conduct of symptom intervention trial.  If the results are positive, a 
definitive ALLIANCE Phase III trial will be conducted.  The legacy group NCCTG, now ALLIANCE have conducted and 
published the largest body of evidence in P-APS and CIPN.  Well established methodologies as well as correlative studies 
from the NCCTG experience will be used to further enhance the design of the Phase III trial. Given the straightforward 
intervention schema and the high incidence of P-APS, rapid accrual to this trial is anticipated. 
 
Other support for this project:  Currently none.