NCT02504892

Everolimus Therapy in People With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer

Phase 2 Study of Everolimus Therapy in Patients With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

Background: \- Research has shown that the drug everolimus can stop cancer cells from growing. It is approved for people with advanced kidney cancer. Researchers want to see if it also helps people with two other types of kidney cancer. Objective: \- To see if everolimus is safe and effective in people with Birt-Hogg-Dube Syndrome (BHD)-associated kidney cancer or sporadic (nonfamilial) chromophobe renal cancer. Eligibility: \- People ages 18 and over with BHD-associated kidney cancer or advanced sporadic chromophobe renal cancer. Design: * Participants will be screened with: * Medical history, physical exam, and blood and urine tests. * Computed tomography (CT) scan or magnetic resonance imaging (MRI) scan. They will lie in a machine that takes pictures of their chest/abdomen/pelvis. * They may also be screened with: * Another scan, of the brain or neck. * Bone scan. * Positron emission tomography scan with fludeoxyglucose (FDG-PET). * Heart and lung tests. * Tests for hepatitis. * Participants will take a tablet once a day by mouth for up to a year. They will keep a diary of when they take the tablet and any symptoms. * During the study, participants will have physical exams and urine and blood tests. They will have scans of the chest/abdomen/pelvis. They may have FDG-PET and bone scans. * Participants will have tests for hepatitis and may have a tumor sample taken. * Participants will have a follow-up visit 4-5 weeks finishing taking the drug. They will have a physical exam and blood tests. They may have scans and/or hepatitis tests. * Participants will be called about every 3-6 months after the study ends to see how they are doing

Detailed description

Background: * Birt-Hogg-Dube (BHD) is a hereditary cancer syndrome with clinical manifestations including cutaneous fibrofolliculomas, lung cysts/pneumothorax, and renal cell carcinoma (RCC). RCC occurs in approximately 30% of patients with BHD. It presents at an early age of onset and is commonly bilateral and multifocal. * Tumors associated with BHD can have variable histology, however approximately 85% of these tumors have a chromophobe component (either alone or part of a hybrid tumor mixed with elements of oncocytoma). * The current management includes surgical resection with partial nephrectomy when tumors reach 3 cm. While significant morbidity can be associated with repeat, partial nephrectomy with this approach, most patients can maintain renal function and do not develop systemic disease. There are no proven systemic therapy options for BHD to date. * Germline mutations in the gene Folliculin (FLCN) are the genetic hallmark of BHD and can be found in greater than 90% of patients. FLCN is believed to function like a classic tumor suppressor gene with a second hit in the wild type allele (somatic mutation or loss of heterozygosity) occurring in the majority of renal tumors. * BHD is in the family of hamartomatous disorders similar to Tuberous Sclerosis Complex (TSC) and Cowden Syndrome, and studies have found activation of the phosphoinositide 3-kinase (PI3K)/mTOR pathway in BHD renal tumors. FLCN is believed be part of a complex that interacts with 5' AMP-activated protein kinase (AMPK) and is involved with regulation of mTOR activity. In vitro and in vivo models of FLCN loss demonstrate activation of both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). * Preclinical data from conditional FLCN knockout mice demonstrate that treatment with sirolimus can reverse renal manifestations. * We hypothesize that mTOR inhibition with everolimus treatment will be clinically active in BHD associated RCC. Objectives: -To determine the overall response rate with everolimus treatment in subjects with BHD-associated renal tumors. Eligibility: -Patients with renal cell carcinoma (RCC) associated with Birt-Hogg-Dube Syndrome (BHD). Design: * This is an open label, phase II study to evaluate the efficacy and safety of everolimus therapy in patients with BHD associated renal tumors. Up to 16 evaluable patients will be enrolled. * Tumor response rate will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) and efficacy analysis will be done. * Secondary endpoints will evaluate growth rates (cm/year) while on therapy. * Additionally, reduction in the size of lung cysts and cutaneous fibrofolliculomas will be evaluated.

Conditions

• Renal Cancer
• Birt-Hogg-Dube Syndrome

Interventions

Type	Name	Description
DRUG	Everolimus	Everolimus is a commercial agent and is supplied by Novartis.

Timeline

• Start date: 2015-07-21
• Primary completion: 2018-04-17
• Completion: 2018-04-17
• First posted: 2015-07-22
• Last updated: 2019-03-22
• Results posted: 2019-03-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study