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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

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ClinicalTrials.gov Identifier: NCT01130519
Recruitment Status : Recruiting
First Posted : May 26, 2010
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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.
  • 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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : June 30, 2019


Arm Intervention/treatment
Experimental: 1
All patient will be receiving fixed starting dose of bevacizumab (10 mg /kg IV every 2 weeks) and erlotinib (150 mg/day PO)
Drug: Bevacizumab
Commercially available. Administered by intravenous infusion.
Drug: Erlotinib
Commercially available. Administered orally



Primary Outcome Measures :
  1. Overall response rate [ Time Frame: 4-5 years ]
    Proportion of patients whose tumors shrunk after therapy


Secondary Outcome Measures :
  1. Progression-free survival, duration of response, and overall survival. [ Time Frame: 4-5 years ]
  2. Effect on potential biomarkers of angiogenesis in plasma such as VEGF and soluble VEGFR2. [ Time Frame: 4-5 years ]
  3. Determine the extent of TGF upregulation and/or EGFR expression/ pathway activation in leiomyomas/ RCC tumor tissue. [ Time Frame: 4-5 years ]
  4. Prevalence of somatic FH mutations/inactivation in patients with sporadic papillary RCC. [ Time Frame: 4-5 years ]
  5. Effect on circulating endothelial cells and endothelial progenitor cells. [ Time Frame: 4-5 years ]
  6. 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 ]
  7. Effect on HLRCC associated uterine and skin leiomyomas. [ Time Frame: 4-5 years ]


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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 outlined in RECIST 1.1
  • 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

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 and/or has no evidence of disease for greater than or equal to 2 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.

INCLUSION OF WOMEN AND MINORITIES:

Both men and women and members of all races and ethnic groups are eligible for this trial.


Information from the National Library of Medicine

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


Contacts
Contact: Erin N Purcell (301) 402-7913 purcelle@mail.nih.gov
Contact: Ramaprasad Srinivasan, M.D. (240) 760-6251 ramasrin@mail.nih.gov

Locations
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      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ramaprasad Srinivasan, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01130519     History of Changes
Other Study ID Numbers: 100114
10-C-0114
First Posted: May 26, 2010    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Advanced HLRCC
Sporadic Papillary Renal Cell Cancer
Papillary Kidney Cancer
Bevacizumab
Erlotinib
Kidney Cancer
Renal Cell Cancer
Hereditary Leiomyomatosis and Renal Cell Cancer
HLRCC

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Leiomyomatosis
Skin Neoplasms
Uterine Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Leiomyoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Genital Neoplasms, Female
Uterine Diseases
Genital Diseases, Female
Bevacizumab
Erlotinib Hydrochloride
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents