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

NCT01130519 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 10011410-C-0114
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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 computed tomography (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.

Conditions

HLRCC; Sporadic Papillary Renal Cell Cancer

Keywords

Immunotherapy; Biomarker; Kidney Cancer; Renal Cell Cancer; Hereditary Leiomyomatosis and Renal Cell Cancer; HLRCC

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Participants whose tumors regressed (Complete Response (CR) plus Partial Response (PR)) after therapy as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the longest diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Data shown with 95% confidence intervals.

  Every 8 weeks during the first 32 weeks and every 12 weeks thereafter, a median of 64.3 months

Secondary Outcomes (3)

• Progression-free Survival

  Amount of time subject survives without disease progression after treatment; a median of 15 months.

• Duration of Response

  Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented; a median of 19 months.

• Overall Survival (OS)

  Time from the date of study enrolment until time of death; a median of 29.3 months.

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 133 months and 13 days; and 119 months and 2 days for the first and second group respectively.

Study Arms (1)

1 - Bevacizumab and Erlotinib

EXPERIMENTAL

All patients will be receiving fixed starting dose of bevacizumab (10 mg/kg intravenous (IV) every 2 weeks) and erlotinib (150 mg/day by mouth (PO)

Drug: Bevacizumab; Drug: Erlotinib

Interventions

Bevacizumab DRUG

Commercially available. Administered by intravenous infusion.

Also known as: Avastin

1 - Bevacizumab and Erlotinib

Erlotinib DRUG

Commercially available. Administered orally.

Also known as: Tarceva

1 - Bevacizumab and Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all the following criteria to be eligible for study enrolment:
• Diagnosis of advanced renal cell cancer (RCC) associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) (cohorts 1 \& 3) or sporadic/non-HLRCC papillary RCC (cohort 2 \& 4)
• Measurable disease outlined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• No more than two prior regimens targeting the vascular endothelial growth factor (VEGF) pathway; no prior bevacizumab therapy
• Age greater than or equal to 18 years.
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
• Patients must have normal organ and marrow function as defined below: white blood cell (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, aspartate aminotransferase (AST) and alanine aminotransferase (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 or equal to 5 times the upper limit of reference range if considered to be related to liver or bone metastases by the principal investigator (PI)

You may not qualify if:

• 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, gastrointestinal (GI) perforation/fistula, intra-abdominal 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 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 human immunodeficiency virus (HIV)-positive and requiring antiretroviral therapy (due to the risk of potential drug interactions)
• Concomitant therapy with potent inhibitors of Cytochrome P450 3A4 (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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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. doi: 10.1136/jmg.2005.033506. Epub 2005 Jun 3.

  PMID: 15937070 BACKGROUND

• Lehtonen HJ, Kiuru M, Ylisaukko-Oja SK, Salovaara R, Herva R, Koivisto PA, Vierimaa O, Aittomaki 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. doi: 10.1136/jmg.2005.036400. Epub 2005 Sep 9.

  PMID: 16155190 BACKGROUND

• Merino MJ, Torres-Cabala C, Pinto P, Linehan WM. The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am J Surg Pathol. 2007 Oct;31(10):1578-85. doi: 10.1097/PAS.0b013e31804375b8.

  PMID: 17895761 BACKGROUND

• Srinivasan R, Gurram S, Singer EA, Sidana A, Al Harthy M, Ball MW, Friend JC, Mac L, Purcell E, Vocke CD, Ricketts CJ, Kong HH, Cowen EW, Malayeri AA, Shih JH, Merino MJ, Linehan WM. Bevacizumab and Erlotinib in Hereditary and Sporadic Papillary Kidney Cancer. N Engl J Med. 2025 Jun 19;392(23):2346-2356. doi: 10.1056/NEJMoa2200900.

  PMID: 40532152 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell; Hereditary leiomyomatosis and renal cell cancer

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Ramaprasad Srinivasan
• Organization: National Cancer Institute

ramasrin@mail.nih.gov

240-760-6251

Study Officials

• Ramaprasad Srinivasan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: May 6, 2010
• Primary Completion: April 12, 2022
• Study Completion: June 8, 2022
• Last Updated: February 21, 2025
• Results First Posted: August 1, 2023

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)