Consent To Participate - SS1 (dsFv)-PE38 Anti-Mesothelin Immunotoxin

Latest Amendment Approved: Amend A 12/18/00

Summary Last Modified on 2/2002

INTRODUCTION

First, we want you to know that:

• Taking part in NIH research is entirely voluntary

• You may choose not to take part, or you may withdraw from the study at any time. In either case, you will not lose any benefit to which you are otherwise entitled. However, to receive care at the NIH, you must be taking part in a study or be under evaluation for study participation.

• You may receive no benefit from taking part. The research may give us knowledge that may help people in the future.

Your physician has determined that you are eligible for a study of a new experimental agent, SS1 (dsFv) - PE38, which is being studied in parties with certain cancers that have recurred or progressed (continued to grow) despite prior treatments.

Mesothelin is a protein normally produced by cells lining body cavities which has been found also on cells in several types of cancer. SS1 binds very tightly to mesothelin. Pseudomonas exotoxin (PE) is a protein made by bacteria which can kill human cells if it gets inside. The experimental agent SS1 (dsFv)-PE38 is composed of a stable form of SS1 and a portion of the PE. It is hoped that the SS1 will attach to the cancer cells and permit entry of the PE, killing the cells.

The purposes of this study are to determine the side effects and highest tolerated dose of SS1 (dsFv)-PE38, to determine the blood levels of the drug, and to look for evidence of effectiveness of the agent against these cancer types.

Description of Research Study

If you choose to enter this study, you will have a comprehensive review of your medical history, a complete physical examination, and certain laboratory tests (blood and urine) to record your current condition. A test will be performed to check the condition of your heart.

The SS1 (dsFv)-PE38 will be given continuous by vein for ten days (e.g., Monday through the following Wednesday). Your weight and vital signs (temperature, heart and breathing rate, and blood pressure) will be recorded to look for side effects during treatment, weekly for two weeks and whenever needed if side effects occur. A test to measure any response of your immune system to the drug will be obtained. Tests to measure the effect of SS1(dsFv)-PE38 on your tumor (such as X-ray or CT scan) will be repeated four weeks after each treatment.

Any side effect, symptom, or other change must be reported immediately to your doctor or nurse, whether or not is seems related to the drug.

If you and your doctor choose to continue, treatment may be repeated, depending on side effects every four weeks up to a maximum of four treatments. Physical exams and blood tests to check for side effects will be repeated. Blood will also be drawn in later courses to measure levels of SS1(dsFv)-PE38. The heart tests will be repeated after 3 courses of treatment, or sooner if you stop treatment. Your condition will be recorded every three months subsequently.

Risks or Discomforts of Participation

As with any new drug, previously unknown side effects are possible. Side effects reported with similar drugs include:

• Allergic reactions may include skin redness, itching or hives, chills and fever, wheezing or difficulty breathing, and may be life threatening or even fatal. In order to give treatment immediately for any allergic reaction, you must remain under observation for four hours after the first dose of each treatment

• Changes in liver function generally detected by blood tests.

• Retention of fluid in the body with weight gain, puffiness, and difficulty breathing which may require intensive care using a respirator.

• Muscle Injury with aching, fatigue, and possible effect on heart muscle.

• Irritation of the skin, possibly where the drug was infused.

Blood tests can cause discomfort, bruising or bleeding at the site of the needle. Up to a pint, or one unit, of blood may be drawn every 6 weeks while on protocol, for protocol purposes. To avoid multiple punctures, central lines will be placed in most patients. The risks of having central lines include bleeding, infection, and collapse of the lung. Close monitoring is required for patients receiving investigational agents; you should not participate if you are unable or unwilling to meet the requirement of the study. Your physician will take precautions to reduce the risk of side effects and will treat them in any occur.

Women may not participate in this study if they are pregnant or breast-feeding, and must use a reliable method of birth control while participating in the study. If you are a woman of childbearing age, you may be given a pregnancy test. If you suspect that you have become pregnant during the study, notify your doctor immediately.

If you do not respond to therapy, you may be asked to have a biopsy at the end of the study to help determine if the mesothelin antigen is gone from your cancer cells and if that is the reason why you did not respond. You have a right to refuse this biopsy.

The expected length of hospitalization is at least 12 days, since all infusions will occur within the hospital. However, you will be able to walk around during this time and will not be confined to bed.

Potential Benefits of Participation

The study drug may kill cancer cells, causing your tumor to shrink. However, you may not benefit from participation in this study. Information gained during this study may benefit other patients with cancer.

Research Subject's Rights

Your participation in this study is entirely voluntary. You may withdraw from the study at any time without penalty or loss of benefits to which you are otherwise entitled. Any new findings that might cause you to change your mind about participating in this study will be reported to you as soon as possible.

Your treatment will be terminated if you develop excessive side effects, an allergic reaction, or another unrelated medical problem, if your tumor grows despite treatment, or if you are unable to cooperate with the study procedures.

Blood and tissue samples collected from you may be stored and used in the future to study scientific questions related to this protocol. If there are any risks to you or your family associated with these scientific studies which are not covered in this consent form, your consent must be obtained before such studies are performed.

If you have questions about the procedures, contact:

Robert J. Kreitman, M.D.: 301-496-6947
or
Diana O'Hagan: 301-496-9458

** RE-POSTED APRIL 30, 2002 **