Clinical Trial: 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
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: 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
Brief Summary:
Background:
- At the present time, there are no drugs that have been proven to work in patients with papillary kidney cancer that has spread (metastasized) beyond the kidneys. Researchers are interested in determining whether the combination of the drugs bevacizumab and erlotinib can be used to treat metastatic papillary kidney cancer.
- Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is an inherited type of papillary kidney cancer (it runs in families). Papillary kidney cancer can also occur sporadically, or without a family connection. More research is needed to determine whether treatments for papillary kidney cancer, such as bevacizumab and erlotinib, work in inherited or sporadic types of kidney cancer, and if so, whether there are any differences.
Objectives:
-To determine the effectiveness of the combination of bevacizumab and erlotinib as a treatment for patients with (1) metastatic HLRCC kidney cancer and (2) metastatic kidney cancer not associated with HLRCC (or sporadic papillary RCC).
Eligibility:
- Individuals 18 years of age or older who have been diagnosed with papillary kidney cancer that has spread beyond the kidneys.
- Participants may have either HLRCC or sporadic papillary kidney cancer.
Design:
- Participants will be screened with a full medical history, physical examination, blood and urine tests, and CT and other scans to evaluate tumor size and treatment options.
- Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a familial cancer syndrome characterized by a propensity for developing renal cancer, uterine and cutaneous leiomyomas.The kidney cancer associated with HLRCC is associated with HLRCC is clinically aggressive and is characterized by unique histopathologic features that are sometimes described as type2 papillary RCC.
- Germline mutations in fumarate hydratase (FH) are the genetic hallmark of HLRCC. Mutational inactivation of FH has been shown to result in VHL-independent upregulation of hypoxia inducible factor (HIF) and its downstream transcriptional targets.
- The recognition that HIF upregulation may play an important role in the formation and propagation of renal cancer associated with HLRCC suggests that interventions directed against components of this pathway, such as VEGF and TGF-alpha/EGFR, may be of benefit in this patient population.
- We propose to test the hypothesis that dual VEGF/EGFR blockade with bevacizumab/erlotinib is likely to be clinically active in patients with HLRCC associated RCC as well as those with sporadic papillary sporadic RCC.
- Diagnosis of advanced RCC associated with HLRCC (cohort1) or sporadic/non-
Sponsor: National Cancer Institute (NCI)
Current Primary Outcome: Overall response rate [ Time Frame: 4-5 years ]
Original Primary Outcome: To determine the overall response rate (RECIST) in patients with 1) metastatic RCC associated with HLRCC and 2) metastatic sporadic papillary RCC, treated with a combination of bevacizumab and erlotinib [ Time Frame: 3-6 years ]
Current Secondary Outcome:
- Progression-free survival, duration of response, and overall survival. [ Time Frame: 4-5 years ]
- Effect on potential biomarkers of angiogenesis in plasma such as VEGF and soluble VEGFR2. [ Time Frame: 4-5 years ]
- Determine the extent of TGF upregulation and/or EGFR expression/ pathway activation in leiomyomas/ RCC tumor tissue. [ Time Frame: 4-5 years ]
- Prevalence of somatic FH mutations/inactivation in patients with sporadic papillary RCC. [ Time Frame: 4-5 years ]
- Effect on circulating endothelial cells and endothelial progenitor cells. [ Time Frame: 4-5 years ]
- Evaluate modulation of HIF, VEGF and EGFR pathways in cutaneous leiomyomas (in patients with HLRCC) and in renal tumors following therapy. [ Time Frame: 4-5 years ]
- Effect on HLRCC associated uterine and skin leiomyomas. [ Time Frame: 4-5 years ]
Original Secondary Outcome: -PFS, OS, duration of response; Effect on CEC/CPC; Effect on angiogenesis biomarkers [ Time Frame: 4-7 years ]
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: May 25, 2010
Date Started: May 4, 2010
Date Completion: January 1, 2019
Last Updated: May 13, 2017
Last Verified: January 11, 2017
Detailed Summary:
Background:
Objective:
Primary Objective
-To determine the overall response rate (RECIST) in patients with 1) metastatic RCC associated with HLRCC and 2) metastatic sporadic/non-HLRCC papillary renal cancer treated with a combination of bevacizumab and erlotinib
Eligibility:
