The Novartis drug (PTK) which Dr. Kaelin is trialing in Boston (see VHLFF December 1998) is making good progress through Phase 1. They are doing dose escalations and expect Phase 1 to be completed by the end of 1999. A small number of people with VHL have been added to Phase 1 of the trial under compassionate exemption; more are expected to be invited into Phase 2. Novartis PTK is administered as a pill taken once a day.

Update 2004

Dr. William Kaelin, Dana Farber Cancer Research Institute, 44 Binney Street, Boston, MA 02115 USA; +1 (617) 632-4747; Fax: +1 (617) 632-4381

Another new drug from Sugen, called SU5416, has completed Phase 1 and is entering Phase 3 in colorectal and lung cancer. At the same time, Sugen is conducting phase 2 trials with VHL and other conditions. As with the Novartis drug, SU5416 is based on strategies for suppressing the signal associated with the excessive production of vascular endothelial growth factor (VEGF). It is hoped that SU5416 will inhibit the growth of new blood vessels and hemangioblastomas in patients with VHL and prevent further tumor growth. - See Update 2004

SU5416 was featured on the television magazine 60 Minutes in May. Reporter Ed Bradley followed several people through the Phase 1 trial. The goal of Phase 1 is to determine the toxicity level of the drug, not necessarily to achieve tumor response. All of the 100 subjects in the Phase 1 trial had very advanced cancer and were not expected to live more than one year. At the end of the year, thirty people were alive, some with stable disease and occasionally with tumor response. The worst side effects at highest doses were headaches with nausea and vomiting, which went away when the dosage was reduced. Other side effects observed were mildly painful vein irritations. One person with VHL has been taking SU5416 for only two months so far. Her eye tumor has not yet shrunk, but she is getting symtomatic relief, giving us sufficient hope to induce Sugen to write two new protocols for trying this drug with VHL in Europe and in the US.

The VHL trial in Europe will be held under one primary investigator, Professor Adrian Harris, in Oxford, UK. People who are interested should contact one of the doctors listed below.

The multicenter VHL trial in the US has just opened its first site: Dr. David Palchak, Aroyo Grande (near San Luis Obispo), California. The contact was established initially by the patient, and Sugen is willing to consider enrolling additional investigators to make the drug available more locally for qualified patients. As the process of tumor growth occurs over weeks to years, it is unlikely that long-term clinical benefit will be observed in patients after limited dosing. A patient, therefore, will be eligible to continue to receive the drug after the completion of this Phase, as long as there is good tumor response and there are no unacceptable side effects.

The drug is administered in the doctor’s office or hospital two times a week (Monday and Thursday or Tuesday and Friday). It is administered as an intravenous drip and takes about one hour.

People participating in the Sugen study of SU5416 will be required to:

Have a VHL diagnosis verified by DNA at one time during the patient history
Be at least 18 years old, or 16 with consent of a guardian.
Use strong effective (barrier) contraceptives (both men and women) as this class of drugs is expected to harm a developing fetus, and because the effects on sperm exposed to the medication are unknown.

People with any of the following are not eligible for this study:

Has absolute neutrophil count (ANC) < 1,500/mm3; platelet count < 100,000/mm3; hemoglobin < 8.0 g/dL.
Has a significant liver function abnormality manifested by an increase in serum transaminases (AST, ALT) > 3.0 x upper limit of normal, or a total bilirubin > 2.0 mg/dL. Has a significant renal function abnormality (serum creatinine > 2.5 mg/dL or creatinine clearance < 40 mL/min) Is still recovering from a previous VHL treatment.Has had major surgery or another investigational drug within 2-4 weeks prior to enrollmentHas had another anti-angiogenic therapy, or organ transplant.Has a known allergy to Cremophor® or Cremophor®-based drug products, corticosteroids, H1 blockers, or H2 blockers.Has a Karnofsky Performance Status (KPS) <60% Has had a heart attack or severe angina within 6 months prior to the studyHas insulin-dependent diabetes, peripheral vascular disease, or diabetic ulcers.
Has any other acute or chronic medical or psychiatric condition that may interfere with the interpretation of study results.

For further information on SU5416, please contact the team nearest to you:
Note: trials of SU5416 have been halted. See Update 2004 for additional drugs of interest.

- Dr. Adrian Harris, Med Oncology, Churchill Hospital, Headington, Oxford OX3 7LJ England, U.K. Tel: +44 (0)1865 226184; Fax: +44 (0)1865 226179; E-mail: v.berry@icrf.icnet.uk

- Dr. David Palchak, 1184 Grand Avenue, Arroyo Grande, CA, USA, 93420, Tel: +1 (805) 473-8983; Fax: +1 (805) 473-8735; E-mail: dpalchak.pol.net

- Peter Hirth, Executive VP, Drug Research & Development, 230 East Grand Ave., South San Francisco, CA 94080 USA; Tel: +1 (650) 553-8707; Fax +1 (650) 553-8303; E-mail: peter-hirth@sugen.com

As printed in the VHL Family Forum 7:3, September 1999. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.