Recombinant Human Hyaluronidase in Treating Lymphedema in Patients With Cancer

Study Overview
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Brief Summary
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This phase 1-2 trial studies the side effects and the best dose of recombinant human hyaluronidase and to see how well it works in treating lymphedema in patients with cancer. Recombinant human hyaluronidase (r-hu-hyaluronidase, rHuPH20) may reduce limb edema size in patients with lymphedema.

Detailed Description
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This is a phase 1, dose-escalation study followed by a phase 2 study. Phase 1: rHuPH20 subcutaneously (SC) on days 1, 3, 5, and 7 Phase 2: rHuPH20 SC on days 1 to 21

Official Title
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Pilot Phase 1-2 Investigational Study to Assess the Efficacy and Safety of Recombinant Hyaluronidase (rHUPH20) in the Treatment of Secondary Lymphedema Resulting From Local Management of Malignancy

Conditions
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Lymphedema, Malignant Neoplasm

Intervention / Treatment
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* Biological: recombinant human hyaluronidase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 2 Unilateral upper limb secondary lymphedema Must have the ability to understand and the willingness to sign a written informed consent document 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 Must consent to multi-bio-frequency impedance analysis (MFBIA); the details are to be covered in consent Willing to sign consent for skin biopsies and phlebotomy 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 Exclusion Criteria: Pregnant or actively breast-feeding Bilateral upper extremity edema Bilateral manipulation of axilla within the last 24 months Active infections Receiving concomitant treatment for upper extremity lymphedema, or who have received treatment within the last 14 days Known allergic or hypersensitivity reaction to rHUPH20 or any hyaluronidase extracts Receiving 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 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 Unable or unwilling to self/home administer subcutaneous experimental drug; study nurse or physician will train individuals on proper administration techniques Unwilling or incapable of maintaining a detailed log of number of injections, the date, time and site of administration Active malignancy; those undergoing active treatment for malignancy in the adjuvant setting are eligible; treatment can include chemotherapy, targeted therapy or anti-hormonal therapy At least 4 weeks removed from surgery or radiation in affected arm Primary lymphedema; if edema can be explained by systemic or congenital illnesses, that patient will not be eligible for this study 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 Must not have received any investigational agents within 30 days prior to commencing study treatment Active thrombophlebitis Pulmonary edema, congestive heart failure or pulmonary embolus
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: recombinant human hyaluronidase<br>Phase 1. 450 units recombinant human hyaluronidase (rHuPH20) administered SC on days 1, 3, 5, and 7 Phase 2: 900 units recombinant human hyaluronidase (rHuPH20) administered SC on days 1 to 21 | Biological: recombinant human hyaluronidase<br>* Given SC<br>* Other names: rHuPH20;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related Adverse Events | Reported as any untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered recombinant human hyaluronidase, and judged possibly, probably, or definitely related to treatment | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Forearm Volume | Number of patients that achieve a clinically significant reduction in lymphedema, assessed as a 20% reduction in excess forearm volume | Up to 1 year |