Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

OBJECTIVES:

Primary

- Determine the efficacy of duloxetine hydrochloride in cancer patients with painful
chemotherapy-induced (taxane or platinum agent) peripheral neuropathy.

Secondary

- Determine the influence of this drug on peripheral neuropathy-related functional status
and quality of life of these patients.

- Describe the differences in duloxetine hydrochloride efficacy when used to treat pain
caused by chemotherapy-induced peripheral neuropathy based on the neurotoxic drug and
class.

OUTLINE: This is a randomized, double-blind, placebo-controlled, crossover study. Patients
are stratified according to prior neurotoxic agent (paclitaxel vs oxaliplatin vs other
taxane agents without paclitaxel vs platinum agents [cisplatin] without oxaliplatin) and
high risk for developing painful chemotherapy-induced peripheral neuropathy (no vs yes).
Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6.
After a 1-week rest period, patients cross over to receive an oral placebo once or
twice daily in weeks 8-13.

- Arm II: Patients receive an oral placebo once or twice daily in weeks 1-6. After a
1-week rest period, patients cross over to receive oral duloxetine hydrochloride once
or twice daily in weeks 8-13.

Patients complete pain and quality of life questionnaires, including the BPI-SF once weekly
and FACT/GOG-NTX and EORTC QLQ-C30 questionnaires, in weeks 1, 6, 8, and 13.

After completion of study treatment, patients are followed for 2 weeks.

DISEASE CHARACTERISTICS:

- Diagnosis of cancer

- CNS malignancy allowed with the exception of leptomeningeal carcinomatosis

- Must have painful sensory chemotherapy-induced peripheral neuropathy (CIPN) resulting
from prior treatment with single-agent taxane or platinum agents (paclitaxel,
docetaxel, nab-paclitaxel, oxaliplatin, cisplatin) (may not have received drugs from
both classes)

- CIPN > grade 1 as measured by NCI-CTCAE v 4.0

- Average neuropathic pain score ≥ 4

- Patients with the following illnesses known to cause peripheral neuropathy are
eligible, provided they have no evidence of neuropathy from these illnesses:

- Diabetes mellitus

- Peripheral vascular disease

- HIV infection

- Significant degenerative or familial neurologic disorder known to cause
peripheral neuropathy

- No clinical or subclinical neuropathy from nerve compression injuries (i.e., carpal
tunnel syndrome, brachial plexopathy, spinal stenosis, or spinal nerve root
compression)

PATIENT CHARACTERISTICS:

- AST ≤ 3 times upper limit of normal

- Total bilirubin ≤ normal

- Creatinine clearance > 30 mL/min

- Not pregnant or nursing

- Able to take oral or enteral medication

- No history of seizure disorder

- No diagnosis of ethanol addiction or dependence within the past 10 years

- No history of narrow-angle glaucoma

- None of the following:

- History of suicidal thoughts

- Symptoms of or history of schizophrenia, bipolar disease, or a major depression

- Serious eating disorder such as bulimia or anorexia where electrolyte imbalance
is likely

PRIOR CONCURRENT THERAPY:

- At least 3 months since prior and no concurrent taxane or platinum agent

- At least 14 days since prior and no concurrent monoamine oxidase inhibitors or other
antidepressants

- No other prior or concurrent neurotoxic drugs (e.g., vincristine, vinblastine,
cytarabine, thalidomide, bortezomib, carboplatin, or procarbazine)

- No concurrent anticonvulsants

- No concurrent B or E vitamin supplementation in doses greater than the recommended
daily allowance (RDA)

- Centrum (standard formula) and One-A-Day "essential" formula which contain 100%
RDA for vitamins B6, E, and B12 allowed

- Other multivitamins allowed provided they contain no more than 100% RDA of B
vitamins and vitamin E

- No concurrent treatment (pharmacologic) for depression