Photobiomodulation Therapy Using the Realief Therapy System for the Treatment of Chemotherapy-associated Peripheral Neuropathy

The treatments will be administered by a Realief Neuropathy Center therapist. The target
surface area and treatment durations will be dictated by the Realief Therapy protocol
according to their proprietary algorithm, which includes assessment of geographic areas
involved and the degree of neuropathy experienced. For the trial, each patient will be given
18 treatments of 30-minute duration, scheduled every three times weekly. The treatments will
include laser exposure of any or all of 27 differentiated areas of the legs, feet, cervical
spine region and lumbar spine region, for durations of 3 to 30 minutes, based on the symptom
presentation at the time. Power densities will vary from 5 to 12 watts, based on the symptom
presentations through the course of therapy.

Inclusion Criteria:

- Patients will have stable or worsening neuropathy (≥grade 2 CTCAE) after the
completion of chemotherapy, with a presumptive remission. Patients who are interested
in enrollment will have a baseline neuropathy assessment followed by a second
evaluation 1 month later to confirm that the neuropathy is not spontaneously improving
(greater than 10% improvement in their mTNS).

- Patients will be 18 years or older at the time of signing the consent.

- Patients must have GOG performance status of 0, 1, 2, or 3 (see appendix III), and be
able to communicate both their symptoms and report the response to neurologic testing.

- Patients must have recovered from the acute and remediable effects of surgery,
radiation therapy and/or chemoradiotherapy. At least 3 weeks must have elapsed from
the last administration of chemotherapy, and at least three weeks must have elapsed
from the last administration of a complete radiation therapy regimen alone or
chemoradiation therapy.

- Patients with pre-existing neuropathy will be eligible, provided that they have not
previously undergone laser therapy for the treatment of their condition.

- Patients must be sterile or on adequate birth control.

- Patients must have willingly signed an approved consent form, be willing to be
randomized to intervention or sham therapy, and be willing to be blinded from directly
observing therapy. Patients completing sham therapy will be offered Realief Therapy in
conjunction with physiotherapy free of charge.

- Patients must be able to attend therapy at the Realief Neuropathy Center in St. Louis
Park as dictated by the requirements of the protocol (3 times/week for up to 8 weeks
as well as once 8 weeks following the completion of therapy) AND be evaluated at the
University of Minnesota's Gynecologic Cancer Clinic for study assessments (4 planned
assessments during and after therapy). Every effort will be made to co-ordinate these
visits with routine health maintenance.

- Life expectancy >6 months

Exclusion Criteria:

- Patients who have previously received a laser-based therapy for the treatment of
neuropathy will be considered ineligible.

- Patients with a > 10% improvement from the initial mTNS assessment to the mTNS
assessment at the time of study enrollment (four weeks from the original assessment).

- Patients with evidence of direct tumor involvement of the nervous system (central or
peripheral) will be considered ineligible.

- Patients who are pregnant will be considered ineligible. Class 4 lasers have been
inadequately studied in this setting to conclude that there is no risk to a developing
fetus.

- Patients with the inability to tolerate therapy or blinding due to co-morbid medical
or psychiatric illness.

- Patients in active treatment of cancer will not be considered eligible.