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
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|ClinicalTrials.gov Identifier: NCT01130519|
Recruitment Status : Recruiting
First Posted : May 26, 2010
Last Update Posted : December 5, 2018
- 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.
-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).
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|HLRCC Metastatic Papillary RCC||Drug: Bevacizumab Drug: Erlotinib||Phase 2|
Hide Detailed Description
- 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.
-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
- Diagnosis of advanced RCC associated with HLRCC (cohort1) or sporadic/non-HLRCC papillary RCC (cohort2)
- ECOG PS 0-2
- Measurable disease as outlined in RECIST 1.1
- No history of major bleeding, recent or active myocardial ischemia, GI perforation, cerebrovascular accidents or other significant intercurrent illness
- No coagulopathy or bleeding diathesis
- No recent surgery (< 4 weeks or inadequately healed surgical scars)
Adequate organ function:
- Adequate liver function (total bilirubin less than or equal to 1.5 mg/dL or < 3 times the upper limit of normal (ULN) in subjects with Gilbert s disease, and AST/ ALT less than or equal to 2.5 times the ULN)
- Adequate renal function (creatinine less than or equal to 2.0 times the ULN or creatinine clearance > 30 mL/min)
- Neutrophils >1500/microL and platelets >100,000
- No brain metastases
- No more than 2 prior regimens containing a VEGF-pathway inhibitor; no prior bevacizumab
- Ability to understand and sign informed consent
- Patients will receive a fixed dose of bevacizumab (10mg/kg IV every 2 weeks) and erlotinib (150mg/day po). Dose reductions and drug interruptions for unacceptable toxicity will be allowed.
- Patients will be evaluated for response every 8 weeks using RECIST criteria
- The study is based on an open label Simon two-stage minmax design in two cohorts, 1) cohort 1- patients with HLRCC, and 2) cohort 2-patients with sporadic papillary RCC. In each cohort, 13 patients will be accrued in the first stage and will accrue a maximum of 20 patients. Accrual into and analysis of the two cohorts will be independent.
- Following completion of accrual to cohorts 1 and 2, the study was expanded to include two additional cohorts- Cohort 3 (HLRCC patients and Cohort 4 (patients with sporadic/non HLRCC papillary RCC) to better estimate the overall response rate and to perform additional exploratory biomarker analyses. Up to 20 additional evaluable patients will be included in each of these cohorts.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||85 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||May 4, 2010|
|Estimated Primary Completion Date :||January 1, 2019|
|Estimated Study Completion Date :||January 1, 2020|
All patient will be receiving fixed starting dose of bevacizumab (10 mg /kg IV every 2 weeks) and erlotinib (150 mg/day PO)
Commercially available. Administered by intravenous infusion.
Commercially available. Administered orally
- Overall response rate [ Time Frame: 4-5 years ]Proportion of patients whose tumors shrunk after therapy
- Progression-free survival, duration of response, and overall survival. [ Time Frame: 4-5 years ]Median amount of time subject survives without disease progression after treatment
- Effect on potential biomarkers of angiogenesis in plasma such as VEGF and soluble VEGFR2. [ Time Frame: 4-5 years ]Correlation between treatment and potential biomarkers such as VEGF and soluble VEGFR2
- Determine the extent of TGF upregulation and/or EGFR expression/ pathway activation in leiomyomas/ RCC tumor tissue. [ Time Frame: 4-5 years ]EGFR expression/ pathway activation in leiomyomas/ RCC tumor tissue
- Prevalence of somatic FH mutations/inactivation in patients with sporadic papillary RCC. [ Time Frame: 4-5 years ]Correlation between treatment and prevalence of somatic FH mutations
- Effect on circulating endothelial cells and endothelial progenitor cells. [ Time Frame: 4-5 years ]Correlation between circulating endothelial cells and endothelial progenitor cells after treatment
- 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 ]Modulation of HIF, VEGF and EGFR pathways in cutaneous leiomyomas and in renal tumors after therapy
- Effect on HLRCC associated uterine and skin leiomyomas. [ Time Frame: 4-5 years ]Correlation between therapy and skin leiomyomas
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01130519
|Contact: Erin N Purcell||(301) email@example.com|
|Contact: Ramaprasad Srinivasan, M.D.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Ramaprasad Srinivasan, M.D.||National Cancer Institute (NCI)|