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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

2014-08-27 03:13:26 | BioPortfolio

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.

- Participants will receive 28-day treatment cycles of bevacizumab (given intravenously every 2 weeks) and erlotinib (a tablet taken by mouth daily).

- Every cycle, participants will return for regular blood and urine tests. Every other cycle, participants will have imaging scans to assess tumor size and response to treatment. Female participants who have uterine fibroid tumors related to their kidney cancer may have additional scans to assess tumor size and response to treatment.

- Participants will continue to receive treatment on the study until their tumors grow or spread to new areas (disease progression), intolerable side effects develop, a better treatment option becomes available, the study closes, it is unsafe to continue treatment, or the participant decides not to remain in the study.

Description

Background:

- HLRCC is a familial syndrome characterized by a propensity for developing renal cancer, uterine and cutaneous leiomyomas. HLRCC-associated RCC is aggressive, with histopathologic features described as type2 papillary RCC.

- Germline mutations in fumarate hydratase (FH) are the hallmark of HLRCC. Inactivation of FH results in VHL-independent HIF upregulation

- Interventions directed against components of the HIF pathway, including VEGF and TGF-alpha/EGFR, may benefit this patient population.

- We propose to test if dual VEGF/EGFR blockade with bevacizumab/erlotinib is active in patients with HLRCC and in sporadic papillary RCC.

Objective:

Primary Objective

-Determine the ORR (RECIST) in 1) HLRCC-associated RCC, 2) sporadic papillary RCC treated with bevacizumab/erlotinib

Secondary Objectives

- Assess PFS, duration of response, and OS

- Investigate the effect of bevacizumab/erlotinib on circulating endothelial cells and endothelial progenitor cells; explore the utility of these markers as surrogates of angiogenesis inhibition

- Investigate the effect of bevacizumab/erlotinib on biomarkers of angiogenesis in plasma such as VEGF and soluble VEGFR2

- Evaluate the prevalence of somatic FH mutations in sporadic papillary RCC

- Determine the extent of TGF-alpha upregulation and/or EGFR expression/pathway activation in leiomyomas/ RCC

- Evaluate modulation of HIF, VEGF and EGFR pathways in leiomyomas and in renal tumors following therapy

- Assess the effect of therapy on HLRCC-associated leiomyomas

Eligibility:

- Advanced HLRCC-associated RCC (cohort1) or sporadic papillary RCC (cohort2)

- ECOG PS 0-2

- Measurable disease

- No major bleeding, recent/ active myocardial ischemia, GI perforation, cerebrovascular accidents or other significant intercurrent illness

- No coagulopathy or bleeding diathesis

- No recent surgery (< 4 weeks or inadequately healedscars)

- Total bilirubin less than or equal to 1.5 mg/dL or < 3 x upper limit of normal (ULN) in subjects with Gilbert's disease, and AST/ ALT less than or equal to 2.5 x ULN

- Creatinine less than or equal to 2.0 x ULN or creatinine clearance > 30 mL/min

- Neutrophils > 1500/microL and platelets > 100,000

- No brain metastases

- 0- 2 prior regimens containing a VEGF-pathway inhibitor; no prior bevacizumab

- Ability to understand and sign informed consent

Design:

- Patients will receive a fixed dose of bevacizumab (10mg/kg IV every 2 weeks) and erlotinib (150mg/day po).

- RECIST response evaluation every 8-12 weeks

- Open label Simon two-stage minmax design stratified into two cohorts, 1) cohort 1- HLRCC, and 2) cohort 2-sporadic papillary RCC. Each cohort will independently accrue13 patients in the first stage and a maximum of 20 patients.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

HLRCC

Intervention

Bevacizumab, Erlotinib

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:13:26-0400

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