Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

PRIMARY OBJECTIVES: I. To obtain pilot data regarding the possible effect of pregabalin on
pain related to paclitaxel-associated acute pain syndrome (P-APS). SECONDARY OBJECTIVES: I.
To obtain pilot data regarding the possible effect of pregabalin on paclitaxel-induced
peripheral neuropathy. II. To obtain pilot data regarding the possible relative toxicities
related to pregabalin therapy in this study situation. TERTIARY OBJECTIVES: I. To
characterize neurological testing abnormalities that might occur with the P-APS, and to
evaluate neurological testing abnormalities during the period of the longer-term
chemotherapy-induced peripheral neuropathy (CIPN). II. To determine the PRO incidence and
characteristics of, and change in, P-APS and paclitaxel induced more chronic CIPN over
several cycles. These data will serve to confirm the results obtained in our previous natural
history study N08C1. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I:
Patients receive pregabalin orally (PO) twice daily (BID), beginning on the first night of
chemotherapy, for 12 weeks and then once daily (QD) for 1 week. ARM II: Patients receive
placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1
week. After completion of study treatment, patients are followed up every 30 days for 6
months.

Inclusion Criteria:

- Age > or equal to 18 years

- Ability to complete questionnaires by themselves or with assistance Paclitaxel at a
dose of 80 mg/m^2 given, in the adjuvant setting, every week for a planned course of
12 weeks without any other concurrent therapy

- Paclitaxel at a dose of 80 mg/m2 given, in the adjuvant (postoperative or
neo-adjuvant) setting, every week for a planned course of 12 weeks without any other
concurrent cytotoxic chemotherapy (trastuzumab and/or other antibody and/or small
molecule treatment is allowed, except for PARP inhibitors).

- Life expectancy > 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for
women of childbearing potential only (per clinician discretion)

Exclusion Criteria:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception since this study involves agents that have known genotoxic, mutagenic
and teratogenic effects

- Previous diagnosis of diabetic or other peripheral neuropathy

- Current, planned or previous use, within last 6 months, of gabapentin or pregabalin

- History of allergic or other adverse reactions to gabapentin or pregabalin

- Significant renal insufficiency with a history of a creatinine clearance (CrCL) <
30ml/min

- Prior exposure to neurotoxic chemotherapy

- Seizure history

- Diagnosis of fibromyalgia

- Previous exposure to paclitaxel