Clinical Trials
The list of clinical trials and studies is constantly changing and people are advised to seek out the latest information from your medical specialists or by contacting info@hlrccinfo.org. The following was current at the time of writing this document.
The Natural History Study at the National Institutes of Health
The US-NIH, currently has a Natural History study for individuals who have been diagnosed with HLRCC or who have the clinical symptoms that might imply a possible diagnosis.
If you have an interest in the US-NIH Study, contact:
First point of contact:
Debbie Nielsen, BSN
Genetic Counselor
Urologic Oncology Branch
National Cancer Institute
National Institutes of Health
Bldg. 10, CRC, Rm. 2W-5740
9000 Rockville Pike
Bethesda MD 20892
T: (240) 760-6247
F: (301) 480-2869
Email: Deborah.Nielsen@nih.gov
Debbie will then send details for scheduling to the patient coordinator
Brittany Dawson-Wade (C) currently on extended leave 3rd March, 3023
Replacement Stefania Misul see email below
Patient Care Coordinator III
Clinical Monitoring Research Program Directorate (CMRPD)
Frederick National Laboratory for Cancer Research
Leidos Biomedical Research, Inc.
Support to: Urologic Oncology Branch
National Institutes of Health
10 Center Drive, Room 2-5750
Bethesda, MD, 20892
T: (240) 529-8590
[Email: Brittany.Dawson@nih.gov]
For HLRCC drug trials, please contact
Erin N. Purcell, BSN, RN
Research Nurse Specialist
National Cancer Institute
National Institutes of Health
9000 Rockville Pike
Bethesda MD 20892
T: (240) 858-3933
F: (301) 480-2869
Email: erin.purcell@nih.gov
The following was current at the time of writing this document.
The Natural History Study at the National Institutes of Health
This study started in 2002 is still currently recruiting participants. The study is now seeing new people with HLRCC who have a kidney cyst or a solid tumor and also one new first person from a new family with HLRCC. Other people at risk in HLRCC families should be screened by their local medical centers. The Trial Number was NCT00055627(now obsolete).
UCLA HLRCC Registry and Study
UCLA has created a registry to characterize the burden of HLRCC, determine who is at risk for skin, uterine, adrenal, and kidney manifestations, and help find new cures for this condition. Patients at other centers have successfully had their tumors sent in to make new models of HLRCC kidney cancer. Please contact them at kidneycancer@mednet.ucla.edu
Phase II Pamiparib and Temozolomide
https://clinicaltrials.gov/show/NCT04603365
“A Phase II Study of Pamiparib and Temozolomide for the Treatment of Hereditary Leiomyomatosis and Renal Cell Cancer”
Brief Summary:
Estimated start date: October 24, 2021
This phase II trial investigates how well pamiparib and temozolomide work in treating patients with hereditary leiomyomatosis and renal cell (kidney) cancer. Poly adenosine diphosphate-ribose polymerase (PARPs) are proteins that help repair DNA mutations. PARP inhibitors, such as pamiparib, can keep PARP from working, so tumor cells can’t repair themselves, and they may stop growing. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pamiparib and temozolomide may help treat patients with hereditary leiomyomatosis and renal cell cancer.
Collaborators:
BeiGene www.beigene.com/
Driven To Cure www.driventocure.org/
Phase II Study of Bevacizumab and Erlotinib
http://clinicaltrials.gov/show/NCT01130519
“A Phase II Study of Bevacizumab and Erlotinib in Subjects With Advanced Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) or Sporadic Papillary Renal Cell Cancer”
This clinical trial of bevacizumab (AVASTIN® | Genentech, Inc.) and erlotinib (Tarceva® is ongoing, and is active but not recruiting patients with papillary kidney cancer that has spread (metastasized) beyond the kidneys. Very good interim results have been reported in http://medicalxpress.com/news/2014-11-kidney-cancer-patients-combination-anti-cancer.html Kidney cancer patients respond well to a combination of two existing anti-cancer drugs
In Annual Meeting News W. Marston Linehan, M.D is reported as saying:
“As for HLRCC syndrome, NCI began focusing on this familial kidney cancer syndrome in the 1980s. Researchers learned that these patients develop a particularly aggressive form of type 2 papillary kidney cancer. In addition to raised and painful cutaneous leiomyomas, 90 percent of female patients in these HLRCC syndrome families also develop uterine fibroids.”
“HLRCC is one of the most malignant types of kidney cancer there is,” Dr. Linehan said. “It needs to be detected because it can spread early and can be lethal.”
HLRCC syndrome is caused by an alteration of the Krebs cycle enzyme, fumarate hydratase. In studying this fumarate hydratase pathway in HLRCC, NCI researchers learned that when the fumarate hydratase gene in the cancer cell is damaged, it alters its metabolism significantly, becoming exceptionally dependent on glycolysis and glucose uptake.
“We have developed an approach to treatment that involves using bevacizumab and erlotinib, therapeutic agents that target the vulnerability of this fumarate hydratase pathway in HLRCC patients with advanced kidney cancer,” Dr. Linehan said. “This is currently an ongoing clinical trial, and we are cautiously optimistic about the early results.”
He also reported that blood tests are available to assist clinicians in making a diagnosis by detecting fumarate hydratase (FH) for HLRCC syndrome and folliculin (FLCN) for BHD syndrome.
“In both of these hereditary cancer syndromes, it is important for dermatologists and other clinicians to understand the significance of fibrofolliculomas and leiomyomas,” Dr. Linehan said. “These patients need to be evaluated for the possible presence of kidney cancer when they present with these dermatologic findings.” Listen to W. Marston Linehan, M.D (MP3)
Editor’s Note: Additional drugs will be forthcoming that will target the FH pathway. Stay tuned for more news
Phase I/II Study of Vandetanib and Metformin
https://clinicaltrials.gov/ct2/show/NCT02495103
“Vandetanib in Combination With Metformin in People With HLRCC or SDH-Associated Kidney Cancer or Sporadic Papillary Renal Cell Carcinoma”
Terminated (Vandetanib is no longer available as Sanofi has decided not to provide additional drug. All subjects are off-study.)
This Phase I/II clinical trial of vandetanib (CAPRELSA® | AstraZeneca United States ) and metforminwas for patients with papillary kidney cancer that has spread (metastasized) beyond the kidneys
Phase II Trial of the DNA Methyl Transferase Inhibitor Guadecitabine (SGI-110)
https://clinicaltrials.gov/ct2/show/NCT03165721
A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer
Wild-type gastrointestinal stromal tumor (GIST) is a cancer in the esophagus, stomach, or intestines. It does not respond well to standard chemotherapy or radiation therapy. Most people with GIST are treated with imatinib. But it may not work in many children with GIST. Researchers think the drug SGI-110 may help treat people with GIST, pheochromocytoma and paraganglioma (PHEO/PGL), or kidney cancer related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC).
Phase I Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
https://clinicaltrials.gov/ct2/show/NCT02071862
This phase I trial using CB-839 is recruiting (December, 2015) patients with Fumarate Hydratase (FH)-deficient tumors.
Phase 2 Trial Olaparib with and without AZD1775, AZD5363, and AZD2014 in Treating Patients with Advanced Solid Tumors
https://clinicaltrials.gov/ct2/show/NCT02576444
Researchers at Yale have just opened a clinical trial that they believe specifically addresses the underlying biology of HLRCC. (They are actively looking for HLRCC patients at this time). Their description in lay language: Cancer patients with a family history of FH or SDH mutations, or tumors found to have these mutations. These mutations most typically appear in patients with hereditary kidney cancers including syndromes such as HLRCC. Genetic testing must have been completed that confirms the presence of this mutation. For patients with a history of HLRCC, the investigators at Yale can assist with confirmation of the mutation in the tumor(s). HOW do I get more information? Contact ranjit.bindra@yale.edu or brian.shuch@yale.edu
There is more information in a conversation in Smart Patients.
Treatment of Cutaneous Leiomyomas with Botulinum Toxin
http://clinicaltrials.gov/show/NCT00971620 “Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas with Botulinum Toxin”
This study is completed and NIH has published a result “The use of botulinum toxin to treat painful cutaneous leiomyomas was associated with improved quality of life and with a trend toward improved pain at rest.” Efficacy of Intralesional Botulinum Toxin A for Treatment of Painful Cutaneous Leiomyomas: A Randomized Clinical Trial.
Intravenous Recombinant Human IL-15
http://www.clinicaltrials.gov/ct2/show/NCT01021059
“A Phase I Study of Intravenous Recombinant Human IL-15 in Adults With Refractory Metastatic Malignant Melanoma and Metastatic Renal Cell Cancer”
This study has completed. No results yet published.