Bevacizumab and Erlotinib Hydrochloride in Treating Patients with Hereditary Leiomyomatosis and Advanced Kidney Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and over10-C-0114
NCI-2013-01459, 100114, P10628, NCT01130519

Trial Description


This phase II trial studies how well bevacizumab and erlotinib hydrochloride work in treating patients with hereditary leiomyomatosis and kidney cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Bevacizumab binds to a protein called vascular endothelial growth factor (VEGF) and may prevent the growth of new blood vessels that tumors need to grow. Erlotinib hydrochloride may stop the growth of tumor cells by blocking a protein called epidermal growth factor receptor (EGFR) that is needed for cell growth. Giving bevacizumab and erlotinib hydrochloride may be an effective treatment for hereditary leiomyomatosis and kidney cancer.

Further Study Information


I. To determine the overall response rate (Response Evaluation Criteria in Solid Tumors [RECIST]) in patients with 1) metastatic renal cell cancer (RCC) associated with hereditary leiomyomatosis (HL) RCC and 2) metastatic sporadic/non-HLRCC papillary RCC treated with a combination of bevacizumab and erlotinib (erlotinib hydrochloride).


I. To assess progression-free survival, duration of response, and overall survival.

II. To investigate the effect of bevacizumab/erlotinib on circulating endothelial cells and endothelial progenitor cells and to explore the utility of these markers as surrogates of angiogenesis inhibition.

III. To investigate the effect of bevacizumab/erlotinib on potential biomarkers of angiogenesis in plasma such as VEGF and soluble vascular endothelial growth factor receptor 2 (VEGFR2).

IV. To evaluate the prevalence of somatic fumarate hydratase (FH) mutations/inactivation in patients with sporadic papillary RCC.

V. To determine the extent of transforming growth factor (TGF)-alpha upregulation and/or EGFR expression/pathway activation in leiomyomas/RCC tumor tissue (when available).

VI. To evaluate modulation of hypoxia-inducible factor 1 (HIF), VEGF and EGFR pathways in cutaneous leiomyomas (in patients with HLRCC) and in renal tumors (when tumors are accessible for biopsy) following therapy.

VII. To assess the effect of therapy on HLRCC associated uterine and skin leiomyomas.


Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 3 months thereafter.

Eligibility Criteria

Inclusion Criteria:

Diagnosis of advanced RCC associated with HLRCC (cohort 1) or sporadic/non-HLRCC papillary RCC (cohort 2)

Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan

No more than two prior regimens targeting the VEGF pathway; no prior bevacizumab therapy

Performance status Eastern Cooperative Oncology Group (ECOG) 0-2

White blood cell (WBC) count >= 3,000/uL

Absolute neutrophil count >= 1,500/uL

Platelet count >= 100,000/uL

Serum creatinine =< 2 x upper limit of reference range or creatinine clearance >= 30 ml/min

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of reference range

Total bilirubin < 1.5 x upper limit of reference range (< 3 x upper limit of reference range in patients with Gilbert's disease)

Alkaline phosphatase =< 2.5 x upper limit of reference range (or =< 5 x upper limit of reference range if considered to be related to liver or bone metastases by the principal investigator [PI])

Recovery from acute toxicity of prior treatment for RCC (to =< grade 1 the active version of Common Terminology Criteria for Adverse Events [CTCAE] or to a level permitted under other sections of inclusion/exclusion criteria)

At least 4 weeks from completion of major surgery and a healed surgical incision

Negative pregnancy test (within 7 days of enrollment) in women of childbearing potential

No myocardial infarction, gastrointestinal (GI) perforation/fistula, intraabdominal abscess, cerebrovascular accidents within six months prior to study entry

No coagulopathy or bleeding diathesis

Ability to understand and the willingness to sign a written informed consent document

Archival tissue block or unstained tumor tissue available for correlative studies

Exclusion Criteria:

Prior invasive malignancy of other histology, with the exception of adequately treated basal or squamous cell carcinoma of the skin, or any other malignancy for which the patient does not currently require treatment

Patients with known brain metastases unless treated with an appropriate modality with no evidence of progression/recurrence for > 3 months

Hypertension not controlled by medical therapy (resting systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg on at least two occasions over a 24 hour period despite optimal medical management)

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association grade III or greater), unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

Serious, non-healing wound or ulcer; bone fracture within 3 months prior to study entry

Patient known to be human immunodeficiency virus (HIV)-positive and requiring antiretroviral therapy

Concomitant therapy with potent inhibitors of CYP450 3A4 (e.g. ketoconazole, verapamil etc) or with potent CYP450 1A2 inhibitors (fluoroquinolone antibiotics including ciprofloxacin, levofloxacin, and norfloxacin; ticlopidine, cimetidine, amiodarone, etc.)

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study

All men and women of childbearing potential must be willing to use effective contraception as determined by the principal investigator (including but not limited to abstinence, hormonal contraceptives [birth control pills, injections, or implants], intrauterine device [IUD], tubal ligation, vasectomy) from the time of enrollment to at least six months following the last dose of drug

Any known hypersensitivity to bevacizumab, erlotinib or other excipients of these drugs

Documented baseline proteinuria > 1000 mg/day on 24 hour urine collection; only patients with 1+ or greater proteinuria on urinalysis (UA) and a spot urine protein: creatinine ratio of > 0.5 will undergo a 24 hour urine collection for quantitation of proteinuria

Left ventricular ejection fraction < 40% as measured on transthoracic echocardiogram

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NCI - Center for Cancer Research

  • Genentech Inc.
  • National Cancer Institute
Ramaprasad Srinivasan, Principal Investigator

Trial Sites



National Cancer Institute Urologic Oncology Branch

Ramaprasad Srinivasan
Ph: 240-760-6251

Ramaprasad Srinivasan
Principal Investigator

National Institutes of Health Clinical Center

Ramaprasad Srinivasan
Ph: 240-760-6251

Ramaprasad Srinivasan
Principal Investigator

Link to the current record.
NLM Identifier NCT01130519

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