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

NCT02504892 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 15016615-C-0166
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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 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

Conditions

Renal Cancer; Birt-Hogg-Dube Syndrome

Keywords

Overall Response Rate; Hereditary Cancer Syndrome; mTOR Therapy Naive

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate With Everolimus Treatment.

  Overall best response is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation in Solid Tumors (RECIST) criteria v1.1. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5mm. Note: the appearance of one or more new lesions is also progression. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

  End of treatment: every 12 weeks up to 1 year

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  median follow-up time: 9 months

• Overall Survival (OS)

  From the first day of treatment to the day of death, up to 1 year

• Count of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 8 months and 28 days.

Study Arms (2)

Birt-Hogg-Dube Syndrome

EXPERIMENTAL

Birt-Hogg-Dube Syndrome (BHD)-associated renal tumors

Drug: Everolimus

Sporadic chromophobe renal tumors

EXPERIMENTAL

Sporadic chromophobe renal tumors

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus is a commercial agent and is supplied by Novartis.

Birt-Hogg-Dube Syndrome; Sporadic chromophobe renal tumors

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a clinical diagnosis of Birt-Hogg-Dub (Copyright) Syndrome (clinical features consistent with BHD and /or a germline Folliculin (FLCN) mutation) and the presence of localized, locally advanced or advanced, renal tumor(s).
• Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 70%).
• Patients must have normal organ and marrow function as defined below:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to 100,000/mcL
• total bilirubin less than or equal to 2mg/dL
• Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase(SGOT)/Alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase(SGPT) greater than or equal to 2.5 times institutional upper limit of normal (ULN) (greater than or equal to 5 times ULN in patients with liver metastases)
• creatinine less than or equal to 2.0 times ULN
• creatinine clearance greater than or equal to 30 mL/min/1.73 m(2)
• fasting serum cholesterol less than or equal to 300 mg/dL OR less than or equal to 7.75 mmol/L
• AND
• fasting triglycerides less than or equal to 2.5 times ULN

You may not qualify if:

• No prior therapy with an mTOR-pathway inhibitor.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Patients currently receiving anticancer therapies (including chemotherapy, radiation therapy, antibody based therapy, etc.).
• Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus).
• Patients with known brain metastases unless treated with an appropriate modality with no evidence of progression/recurrence for \>3months
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics, invasive fungal infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with everolimus. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus.
• Uncontrolled diabetes mellitus as defined by hemoglobin A1c (HbA1c) \>8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
• Patients who have any severe and/or uncontrolled medical conditions such as:
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction less than or equal to 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease.
• Symptomatic congestive heart failure of New York heart Association Class III or IV.
• known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) 50% or less of normal and oxygen (O2) saturation 88% or less at rest on room air).
• active, bleeding diathesis.
• Chronic (treatment \> 1 month) or ongoing treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed.
• Patients who have received live attenuated vaccines within 1 week of start of everolimus Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and typhoid vaccine) TY21a typhoid vaccines.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Schmidt LS. Birt-Hogg-Dube syndrome: from gene discovery to molecularly targeted therapies. Fam Cancer. 2013 Sep;12(3):357-64. doi: 10.1007/s10689-012-9574-y.

  PMID: 23108783 BACKGROUND

• Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1977 Dec;113(12):1674-7.

  PMID: 596896 BACKGROUND

• Schmidt LS, Warren MB, Nickerson ML, Weirich G, Matrosova V, Toro JR, Turner ML, Duray P, Merino M, Hewitt S, Pavlovich CP, Glenn G, Greenberg CR, Linehan WM, Zbar B. Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet. 2001 Oct;69(4):876-82. doi: 10.1086/323744. Epub 2001 Aug 30.

  PMID: 11533913 BACKGROUND

MeSH Terms

Conditions

Kidney Neoplasms; Birt-Hogg-Dube Syndrome; Neoplastic Syndromes, Hereditary

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Ramaprasad Srinivasan
• Organization: National Cancer Institute

srinivasanr@mail.nih.gov

301-451-2298

Study Officials

• Ramaprasad Srinivasan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principla Investigator

Study Record Dates

• First Submitted: July 21, 2015
• First Posted: July 22, 2015
• Study Start: July 21, 2015
• Primary Completion: April 17, 2018
• Study Completion: April 17, 2018
• Last Updated: March 22, 2019
• Results First Posted: March 7, 2019

Record last verified: 2019-03

Locations

US (1)