Recombinant Human Hyaluronidase in Treating Lymphedema in Patients With Cancer

PRIMARY OBJECTIVES:

I. Safety. II. Tolerability. III. To determine whether recombinant hyaluronidase
(recombinant human hyaluronidase) (rHUPH20) has a role in treatment of secondary lymphedema
resulting from treatment of malignancy.

SECONDARY OBJECTIVES:

I. To evaluate for histologic and/or biomarker correlates of lymphedema or rHUPH20 response.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive recombinant human hyaluronidase subcutaneously (SC) on days 1, 3, 5, and 7
(Phase I) and then on days 1-21 (Phase II) in the absence of disease progression or
unacceptable toxicity.

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 2

- Unilateral upper limb secondary lymphedema

- Women of child bearing potential must have a documented negative pregnancy test
within 2 weeks prior to day 1 of treatment and agree to use a non-hormonal form of
birth control during the duration of the trial therapy

- Patients, or legal representative, must have the ability to understand and the
willingness to sign a written informed consent document

- Patient or legal representative must agree to blood serum assessment including,
complete blood count (CBC) with differential; comprehensive metabolic panel and serum
osmolality at every sanctioned evaluation; additionally physician may require cardiac
evaluation with echocardiogram, electrocardiogram, brain natriuretic peptide or
urinalysis if deemed appropriate

- Patient or legal representative must consent to multi-bio-frequency impedance
analysis (MFBIA); the details are to be covered in consent

- Patient or legal guardian willing to sign consent for skin biopsies and phlebotomy

Exclusion Criteria:

- Pregnant patients or actively breast-feeding

- Patients with bilateral upper extremity edema

- Patient with bilateral manipulation of axilla within the last 24 months

- Patient with active infections

- Patient undergoing concomitant treatment for upper extremity lymphedema, or who have
received treatment within the last 14 days

- Patient with known allergic or hypersensitivity reaction to rHUPH20 or any
hyaluronidase extracts

- Patient on concomitant diuretics or dihydropyridine class of calcium channel
blockers; if an alternative medication is available, patient can become eligible
after 3 half-lives of drug discontinued and patient remains medically stable

- Patient has grade 2 or greater hypo-albuminemia, serum sodium greater than 150meq/L,
serum osmolality greater than 300mOsm/kg or blood urea nitrate/serum creatinine ratio
greater than 25, within 7 days of screening

- Patient or family is unable or unwilling to self/home administer subcutaneous
experimental drug; study nurse or physician will train individuals on proper
administration techniques

- Patient or caregivers who are unwilling or incapable of maintaining a detailed log of
number of injections, the date, time and site of administration

- Patients with active malignancy; patient undergoing active treatment for malignancy
in the adjuvant setting are eligible; treatment can include chemotherapy, targeted
therapy or anti-hormonal therapy

- Patient should be at least 4 weeks removed from surgery or radiation in affected arm

- Patient with primary lymphedema; if edema can be explained by systemic or congenital
illnesses, that patient will not be eligible for this study

- Patients must not have any concurrent condition which in the investigator's opinion
makes it inappropriate for the patient to participate in the trial or which would
jeopardize compliance with the protocol

- Patients must not have received any investigational agents within 30 days prior to
commencing study treatment

- Patients with active thrombophlebitis

- Patients with pulmonary edema, congestive heart failure or pulmonary embolus