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
Verified October 2014 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
First received: May 25, 2010
Last updated: May 7, 2015
Last verified: October 2014
- 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.
Metastatic Papillary RCC
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- Overall response rate [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Progression-free survival, duration of response, and overall survival. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
- Effect on potential biomarkers of angiogenesis in plasma such as VEGF and soluble VEGFR2. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
- Determine the extent of TGF upregulation and/or EGFR expression/ pathway activation in leiomyomas/ RCC tumor tissue. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
- Prevalence of somatic FH mutations/inactivation in patients with sporadic papillary RCC. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
- Effect on circulating endothelial cells and endothelial progenitor cells. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Effect on HLRCC associated uterine and skin leiomyomas. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||January 2016 (Final data collection date for primary outcome measure)
Patients with HLRCC receiving a fixed starting dose of bevacizumab (10 mg/kg IV every 2 weeks) and erlotinib (150 mg/day PO). Treatment cycles willconsist of 28 days.
Commercially available. Administered by intravenous infusion.
Commercially available. Administered orally
Patients with sporadic papillary RCC receiving a fixedstarting dose of bevacizumab (10 mg/kg IV every 2weeks) and erlotinib (150 mg/day PO). Treatmentcycles will consist of 28 days.
Commercially available. Administered by intravenous infusion.
Commercially available. Administered orally
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Patients must meet all the following criteria to be eligible for study enrolment:
- 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 greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
- No more than two prior regimens targeting the VEGF pathway; no prior bevacizumab therapy
- Age greater than or equal to 18 years.
- Performance status ECOG 0-2
- Patients must have normal organ and marrow function as defined below: WBC count greater than or equal to 3,000/microL, absolute neutrophil count greater than or equal to 1,500/microL, platelet count greater than or equal to 100,000/microL, serum creatinine greater than or equal to 2 times the upper limit of reference range or creatinine clearance greater than or equal to 30 ml/min, AST and ALT less than 2.5 times the upper limit of reference range, total bilirubin less than 1.5 times the upper limit of reference range ( less than 3 x upper limit of reference range in patients with Gilbert s disease), alkaline phosphatase less than or equal to 2.5 times the upper limit of reference range (or less than than or equal to 5 times the upper limit of reference range if considered to be related to liver or bone metastases by the PI)
- Recovery from acute toxicity of prior treatment for RCC (to less than or equal to grade 1 the active version of 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 enrolment) in women of childbearing potential
- No myocardial infarction, 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
- 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 has not required treatment for three years.
- Patients with known brain metastases unless treated with an appropriate modality with no evidence of progression/recurrence for greater than 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 HIV-positive and requiring antiretroviral therapy (due to the risk of potential drug interactions)
- 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; ticlodipine, cimetidine, amiodarone,etc. see Appendix C)
- Pregnant women are excluded from this study because bevacizumab and erlotinib are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, 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 enrolment 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 greater than 1000mg/day on 24 hour urine collection. Only patients with 1+ or greater proteinuria on UA and a spot urine protein:creatinine ratio of greater than 0.5 will undergo a 24 hour urine collection for quantitation of proteinuria.
- Left ventricular ejection fraction less than 40% as measured on transthoracic echocardiogram.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01130519
|National Institutes of Health Clinical Center, 9000 Rockville Pike
|Bethesda, Maryland, United States, 20892 |
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937 |
||Ramaprasad Srinivasan, M.D.
||National Cancer Institute (NCI)
Wei MH, Toure O, Glenn GM, Pithukpakorn M, Neckers L, Stolle C, Choyke P, Grubb R, Middelton L, Turner ML, Walther MM, Merino MJ, Zbar B, Linehan WM, Toro JR. Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet. 2006 Jan;43(1):18-27. Epub 2005 Jun 3.
Lehtonen HJ, Kiuru M, Ylisaukko-Oja SK, Salovaara R, Herva R, Koivisto PA, Vierimaa O, Aittomäki K, Pukkala E, Launonen V, Aaltonen LA. Increased risk of cancer in patients with fumarate hydratase germline mutation. J Med Genet. 2006 Jun;43(6):523-6. Epub 2005 Sep 9.
||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 25, 2010
||May 7, 2015
||United States: Federal Government
Keywords provided by National Institutes of Health Clinical Center (CC):
Sporadic Papillary Renal Cell Cancer
Papillary Kidney Cancer
Renal Cell Cancer
Hereditary Leiomyomatosis and Renal Cell Cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 01, 2015
Carcinoma, Renal Cell
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Neoplasms, Glandular and Epithelial
Neoplasms, Muscle Tissue
Angiogenesis Modulating Agents