Recombinant Human Hyaluronidase in Treating Lymphedema in Patients With Cancer

Lymphedema Clinical Trial

Official title:

Pilot Phase I/II Investigational Study to Assess the Efficacy and Safety of Recombinant Hyaluronidase (rHUPH20) in the Treatment of Secondary Lymphedema Resulting From Local Management of Malignancy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01928030
• Other study ID #: BRS0032
• Secondary ID: NCI-2013-01624BR
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: August 20, 2013
• Last updated: October 20, 2016
• Start date: December 2013
• Est. completion date: November 2015

Study information

• Verified date: October 2016
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

This pilot phase I/II 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 may reduce limb edema size in patients with lymphedema.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Lymphedema
• Malignant Neoplasm
• Neoplasms

Intervention

Biological:
• recombinant human hyaluronidase
Given SC

Locations

Country	Name	City	State
United States	Stanford University Hospitals and Clinics	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Any untoward medical occurrence or worsening of a pre-existing medical condition in a participant, administered the medicinal product in this clinical investigation, which does not necessarily have a causal relationship with this treatment. Physical exam and laboratory analysis will be undertaken weekly to assess participant safety.	Up to 1 year	Yes
Secondary	Detection of a clinically significant loss of excess forearm volume, 20% volume reduction .	The proportion of patient obtaining a clinically significant reduction in lymphedema, 20% reduction in excess forearm volume, at a 95% confidence interval will be reported.	Up to 1 year	No