Precautions; Adverse Events And Complications; Location Of Procedure; Procedural Team - Delcath Systems CHEMOSTAT Mode D'emploi

• A ll components are for single patient use only. Do not reuse, reprocess or
resterilize. Reuse, reprocessing or resterilization may compromise the structural
integrity of the device and/or lead to device failure which, in turn, may result
in patient injury, illness, or death. Reuse, reprocessing, or resterilization may
also create a risk of contamination of the device and/or cause patient infection
or cross-infection, including, but not limited to, the transmission of infectious
disease(s) from one patient to another. Contamination of the device may lead to
injury, illness, or death of the patient.

PRECAUTIONS

• T he CHEMOSAT System is for use only by qualified personnel properly trained and
familiar with the procedure in accordance with the Instructions for Use.
• C aution: The CHEMOSAT System contains natural rubber latex which may cause
allergic reactions.
• W omen who are pre-menopausal (have had a period within the last 12 months)
must receive appropriate hormonal suppression to prevent potential bleeding as
a result of the procedure.
• T he safety and effectiveness of the use of the CHEMOSAT System on pregnant
women and pediatric patients has not been established.
• P atients should be evaluated for gastric acid hypersecretion (e.g., untreated
gastrinoma) and clinically managed as indicated.
• I n order to avoid mis-infusion of the drug into gastrointestinal branches
originating from the hepatic artery, careful angiographic examination is required,
followed by embolization as indicated. During infusion the catheter tip must be
placed distal to the origins of any gastrointestinal branches that may not have
been embolized.
WARNING
If The Perfusion Of Melphalan Cannot Be Isolated From The Systemic
Circulation, The Procedure Must Be Stopped.
• A dequate anticoagulation is required throughout the procedure to prevent
intravascular thrombosis and to assure unimpeded flow through the
extracorporeal circuit and filters. (See Coagulation Control below).
• D uring the procedure, the arterial blood pressure must be closely monitored as
there will be significant hypotensive episodes related to:
o Initial occlusion of the inferior vena cava by the balloons
o The removal of endogenous catecholamines by the filters
Prompt intervention must be administered as described below under Blood
Pressure Control.
• H epatic artery spasm may occur and potentially cause reflux of the infusate into
more proximal non-embolized gastrointestinal branches. In order to avoid such
reflux, the hepatic artery must periodically be checked angiographically for
spasm. To relieve hepatic artery spasm, which occurs infrequently, use a 50-100
mcg/injection of intra-arterial nitroglycerin locally to relieve spasm. If spasm
does not resolve, the procedure must be stopped.
• T he following clinical effects have been observed during the procedure:
o Decreased platelet counts occur in a majority of patients. Transfusion
is required as clinically indicated. The CHEMOSAT System must not be
administered in patients with platelets <75,000 cells/mm
o Decreased hemoglobin occurs in a majority of patients. Transfusion is
required as clinically indicated. The CHEMOSAT System should not be used on
patients with hemoglobin ≤ 10 g/dL.
o Prolongation of activated partial thromboplastin time is an intended effect
of heparin administration during the procedure; however, since removal
of platelets and clotting factors by the filters can increase the risk of
bleeding, anticoagulation must be reversed promptly by the administration
of protamine sulfate, Fresh Frozen Plasma and cryoprecipitate should be
administered as clinically indicated to correct remaining coagulopathy.
The CHEMOSAT System must not be used on patients with uncorrectable
coagulopathies.
o Decreased serum albumin occurs frequently. Specific corrective intervention
is seldom required.
o Decreased blood calcium (hypocalcemia) occurs frequently. As with other
less frequent electrolyte disturbances, replacement is required when
clinically indicated.
o Elevated hepatic transaminases (alanine aminotransferase, aspartate
aminotransferase), with or without hyperbilirubinemia, occur. They are
self-limiting. No intervention is required.

ADVERSE EVENTS AND COMPLICATIONS

In a Phase 3 Ocular and Cutaneous Melanoma Trial, clinically significant (Grade 3-4)
adverse events that were observed in >35% of patients in descending order of
frequency for the CHEMOSAT System that occurred within the first 72 hours after the
procedure were the following:
Platelet count decreased (69 %), Hemoglobin decreased (60%), Blood Albumin
decreased (37.1%), aPTT prolonged (31.0%), Blood Calcium decreased (21.4%),
AST increased (20%), INR increased (20%), Lymphocyte decreased (12.9%), ALT
increased (8.6%), Blood Bilirubin Increased (10 %), Blood Potassium decreased (10
%), Troponin increased (7.1%).

LOCATION OF PROCEDURE

The procedure must be performed in an appropriately equipped interventional
radiology suite with fluoroscopy or an operating room designed and equipped
similarly. Resuscitation personnel, equipment, and medications must be immediately
available.

PROCEDURAL TEAM

The selection of the required procedural team members should be determined by the
facility based on institutional experience and clinical judgment. The operating team
performing the procedure must include, at a minimum:
• A qualified medical/surgical oncologist experienced in the monitoring of
toxicities of chemotherapy and who is responsible for the complete medical
management of the patient, including, but not limited to, pre- and post-
operative care. The medical/surgical oncologist may also be responsible for
monitoring the patient during the immediate post-procedure period.
The medical/surgical oncologist will also play a unique role in communicating
.
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about chemotherapeutic agent (melphalan hydrochloride) and the CHEMOSAT
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