A medical team under Dr. William Kaelin of the Dana Farber Cancer Research Institute is proposing to conduct a Clinical Trial of a new drug which may have promise in constraining the growth of tumors in people with VHL. The trial is going through the final approvals, and is now expected to begin about January 1999.

Progress is never made without pioneers, people who are willing to venture out onto the frontier and open new territory for everyone. The VHL Family Alliance needs people with VHL to apply to participate in this and the other studies that will be starting up over the coming years. It is important that we show the pharmaceuticals that we will do our part to support innovation in management of VHL.

Clinical trials are not for everyone, and we ure you to make an informed decision based on your own personal risks. Younger people who are basically in good health will probably not want to participate in early trials of any description, as we still do not know what long-term risks there may be. But at the same time, we do need pioneers. If no one is willing to sign on for a voyage that risks sailing off the edge of the earth, we will never find the New World. For those among us whose treatment choices are already limited, we urge you to consider becoming a pioneer. No one can promise you that any experimental drug will be the one that will reverse tumor growth, but the chances now are better than ever before. We can promise that as a community we will learn from these studies, and that it will significantly advance progress toward medical management for all of us.

There is a survey form posted on the internet, or people can contact Dr. Kaelin’s team directly at 617-632-4747. Remember that taking this first step is not a final commitment that you will participate, it is an expression of interest. You will be evaluated to determine that you are physically eligible, provided with more detailed information about the risks and potential benefits to you, and then given the opportunity to join the study or not.

This drug is in pill form. It has been specially designed to inhibit vascular endothelial growth factor (VEGF). Dr. Kaelin’s team has been one of the key teams in learning about the function of the VHL protein – what it does normally, and what happens when the normal VHL protein is absent. What we know so far is that when there is too little normal VHL protein in a cell, there are higher levels of VEGF, and VEGF has been found in high concentrations around brain and kidney tumors, both in VHL and in other conditions. We are hopeful that this drug will be effective in limiting the growth of tumors in VHL, and also that it will be helpful against related brain and kidney tumors in the general population. This trial will help to determine whether that is true.

What's the Objective of the Study?

Volunteers are needed to help determine correct dosage levels for this drug, and then to determine if it is effective in stopping tumors. The study will be divided into two parts. The objective of the first portion is to determine what is a therapeutic dose. Participants will be carefully monitored to see if there is an effect on tumor size, or if any side-effects appear. This portion of the study will be limited, and the criteria will exclude many people with VHL. However qualified participants with VHL will be very important in this phase.

The second portion of the trial is meant to determine the effectiveness of this drug, specifically on the tumors of VHL. Two groups of subjects will be included, measuring the effect upon brain tumors and upon kidney tumors. Participants will be monitored to determine whether brain and kidney tumors can be reduced in volume, and new tumors kept from forming. This portion of the trial will begin once sufficient information has been gathered from the initial portion to determine the dose of the drug that is safe and well tolerated. This will possibly occur as early as summer 1999. This second portion of the trial will enroll only VHL patients.

What is the Time Commitment?

People who participate in the second portion of the trial will need to come to Boston for 1-2 days of testing at the beginning of the trial, and then again once a month for 1-2 days. After the fourth month the intervals may be spaced out somewhat longer, but people should plan on monthly visits.

People who are accepted into the study will be required to have DNA testing. It is a requirement that participants have a confirmed diagnosis of VHL, and that they know their mutation. DNA testing is now available through any geneticist in your own area. It is recommended that samples be sent to the University of Pennsylvania testing lab, 1-800-669-2172

Update 2004

Who is Eligible?

The first portion of the trial is restricted to VHL patients with inoperable kidney cancer and no central nervous system lesions (no brain hemangioblastoma, no spinal tumors). This is a common restriction in early trials in general. People with CNS involvement will be considered for the second portion of the trial.

Participants in the second portion of the trial must have

One or more cerebellar hemangioblastoma(s) with a measurable solid component
Or one or more Renal cell carcinoma tumors of less than 3 cm. in size, with or without cerebellar hemangioblastoma
Or people with inoperable kidney cancer, with or without cerebellar hemangioblastoma

All participants must be 18 years or older, in reasonable health (not bed-ridden, not seriously anemic or suffering from other unresolved medical problems). See details in box.

For further information on this study, please contact Dr. Kaelin’s office directly at 617-632-4747, Fax 617-632-4381, or write to Dr. William G. Kaelin, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

What Questions Should I Ask?

The NCI brochure Taking Part in Clinical Trials: What Cancer Patients Need to Know is available free by calling 1-800-4-CANCER, or on the internet at http://cancertrials.nci.nih.gov/

How Can I Get to Boston?

If you are not in the immediate Boston area, there are resources that may be able to assist you.

The National Patient Air Transport Helpline (N-PATH) maintains current data on all known charitable, charitably-assisted, and special discount commercial long-distance air medical transport options. Call the hotline at 1-800-296-1217 (or see http://www.npath.org) to request assistance. We have already contacted them about this study. The operator will take your information and work to assist you.

The Corporate Angel Network (CAN) provides free air transportation for cancer patients traveling to and from recognized treatment centers in the United States without regard to their financial resources. CAN arranges for patients to use empty seats on corporate aircraft operating on business flights. Call 1-914-328-1313 or see http://www.corpangelnetwork.org

The Following Information was correct as of December 1, 1998, but is subject to change:

Who is Eligible?

The first portion of the trial is restricted to VHL patients with inoperable kidney cancer and no central nervous system lesions (no brain hemangioblastoma, no spinal tumors). People with VHL lesions of the brain or spinal cord may be eligible to join the second portion of the study.

Participants in the second portion of the trial must have

One or more cerebellar hemangioblastoma(s) with a measurable solid component
Or one or more Renal cell carcinoma tumors of less than 3 cm. in size (such that they are comfortable that the tumors can be watched and do not require conventional treatment), with or without cerebellar hemangioblastoma
Or people with inoperable kidney cancer, with or without cerebellar hemangioblastoma

All participants must:

Be 18 years or older
Have a Karnofsky performance status of greater than 70. This is a measure of overall well-being, and serves to exclude people who are very feeble (bed-ridden)
Have an essentially normal white blood cell count
Have a hemoglobin greater than 9 g/dl (are not seriously anemic)
Have a platelet count greater than 100 x 109/L
Have liver function tests within 2.5-fold of upper normal limits
Have a serum creatinine less than or equal to 2.0 mg/dL (normal is 1.5)
Or creatinine clearance of an acceptable level (greater than 30 ml/min). This drug is metabolized by the liver and does not rely too heavily on renal excretion, so this is less restrictive than studies for many other drugs.
Have a life expectancy greater than 3 months
Sign a written informed consent

Who will be excluded from the study?

For the second portion of the trial, participants with any of the following conditions will not be eligible:

Prior bone marrow or stem cell transplant

Pregnant, or at risk of becoming pregnant. All participants (male and female) will be required to practice reliable birth control throughout the period of the study.

Other severe or uncontrolled medical issues (uncontrolled diabetes, heart failure, infection etc.)

Acute or chronic liver disease

HIV positive

Disease which might interfere with the absorption of the drug (e.g. gastrointestinal disease that interferes with the absorption of the drug, such as diarrhea from pancreatic insufficiency)

Taking coumadin

Have received any investigational drugs within 4 weeks prior to the start of the study, or have not recovered from the toxic effects of such therapy.

Have had chemotherapy, biological therapy, or immunological therapy within 4 weeks prior to the start of the study, or have not recovered from any side effects of these therapies prior to the beginning of the study

Have had radiation therapy or surgery less than 2 weeks prior to the beginning of the study, or have not recovered from that surgery or radiation

Have active non-VHL malignancies, other than non-melanoma skin cancers

Other VHL-related tumors (other than brain or kidney) that require treatment at the time of study entry.

As printed in the VHL Family Forum 6:4, December 1998. For permission to reprint, please contact VHL Family Alliance, info@vhl.org.