Ignite Creation Date:
2024-05-06 @ 7:16 AM
Last Modification Date:
2024-10-26 @ 11:46 AM
Study NCT ID:
NCT02504892
Status:
TERMINATED
Last Update Posted:
2019-03-22
First Post:
2015-07-21
Brief Title:
Everolimus Therapy in People With Birt-Hogg-Dube Syndrome BHD-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase 2 Study of Everolimus Therapy in Patients With Birt-Hogg-Dube Syndrome BHD-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer
Status:
TERMINATED
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study was terminated due to slow insufficient accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 chestabdomenpelvis
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 chestabdomenpelvis 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 andor hepatitis tests
Participants will be called about every 3-6 months after the study ends to see how they are doing
- 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 chestabdomenpelvis
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 chestabdomenpelvis 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 andor 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 cystspneumothorax 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 PI3KmTOR 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 cmyear while on therapy
Additionally reduction in the size of lung cysts and cutaneous fibrofolliculomas will be evaluated
Birt-Hogg-Dube BHD is a hereditary cancer syndrome with clinical manifestations including cutaneous fibrofolliculomas lung cystspneumothorax 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 PI3KmTOR 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 cmyear while on therapy
Additionally reduction in the size of lung cysts and cutaneous fibrofolliculomas will be evaluated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 15-C-0166 | None | None | None |