Lymphedema, Malignant Neoplasm
Conditions
Brief summary
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
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
Interventions
BIOLOGICALrecombinant human hyaluronidase
Given SC
Sponsors
National Cancer Institute (NCI)
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related Adverse Events | Up to 1 year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Forearm Volume | Up to 1 year | Number of patients that achieve a clinically significant reduction in lymphedema, assessed as a 20% reduction in excess forearm volume |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hyaluronidase, Recombinant Human Patients receive recombinant human hyaluronidase 450 units or 900 units SC on days 1, 3, 5, and 7 (Phase 1) and then on days 1 to 21 (Phase 2) in the absence of disease progression or unacceptable toxicity. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Hyaluronidase, Recombinant Human |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
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
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 450 Units Recombinant Human Hyaluronidase (rHuPH20) | Treatment-related Adverse Events | 1 Participants |
Secondary
Reduction in Forearm Volume
Number of patients that achieve a clinically significant reduction in lymphedema, assessed as a 20% reduction in excess forearm volume
Time frame: Up to 1 year
Population: No participants received 900 units rHuPH20, and the MTD was not determined, so no participants received rHuPH20 at the MTD.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 450 Units Recombinant Human Hyaluronidase (rHuPH20) | Reduction in Forearm Volume | 0 Participants |
| 900 Units rHuPH20 (Days 1, 3, 5, and 7) | Reduction in Forearm Volume | 0 Participants |
| MTD rHuPH20 (Days 1 to 21) | Reduction in Forearm Volume | 0 Participants |