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 :
Active, not recruiting
First Posted : May 26, 2010
Results First Posted : August 1, 2023
Last Update Posted : February 1, 2024
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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.
Condition or disease | Intervention/treatment | Phase |
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HLRCC Sporadic Papillary Renal Cell Cancer | Drug: Bevacizumab Drug: Erlotinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 83 participants |
Allocation: | N/A |
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 |
Actual Study Start Date : | May 6, 2010 |
Actual Primary Completion Date : | April 12, 2022 |
Estimated Study Completion Date : | December 1, 2024 |
Arm | Intervention/treatment |
---|---|
Experimental: 1 - Bevacizumab and Erlotinib
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)
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Drug: Bevacizumab
Commercially available. Administered by intravenous infusion.
Other Name: Avastin Drug: Erlotinib Commercially available. Administered orally.
Other Name: Tarceva |
- Overall Response Rate [ Time Frame: Every 8 weeks during the first 32 weeks and every 12 weeks thereafter, a median of 64.3 months ]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.
- Progression-free Survival [ Time Frame: Amount of time subject survives without disease progression after treatment; a median of 15 months. ]Median amount of time subject survives without disease progression after treatment. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and 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.
- Duration of Response [ Time Frame: 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. ]Duration of overall response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started), 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 diameters of target lesions. 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.
- Overall Survival (OS) [ Time Frame: Time from the date of study enrolment until time of death; a median of 29.3 months. ]Overall survival is defined as the duration of time from the date of study enrolment until time of death estimated using a Kaplan Meier analysis. Participants without a death event will be censored at the date survival assessment was last evaluated (e.g., clinic visit, phone call).
- Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [ Time Frame: 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. ]Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
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)
- Recovery from acute toxicity of prior treatment for RCC (to less than or equal 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 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
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 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
- 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 urinalysis (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.
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
United States, Maryland | |
National Institutes of Health Clinical Center | |
Bethesda, Maryland, United States, 20892 |
Principal Investigator: | Ramaprasad Srinivasan, M.D. | National Cancer Institute (NCI) |
Documents provided by Ramaprasad Srinivasan, M.D., National Cancer Institute (NCI):
Publications:
Responsible Party: | Ramaprasad Srinivasan, M.D., Principal Investigator, National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT01130519 |
Other Study ID Numbers: |
100114 10-C-0114 |
First Posted: | May 26, 2010 Key Record Dates |
Results First Posted: | August 1, 2023 |
Last Update Posted: | February 1, 2024 |
Last Verified: | January 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (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). |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Immunotherapy Biomarker Kidney Cancer |
Renal Cell Cancer Hereditary Leiomyomatosis and Renal Cell Cancer HLRCC |
Carcinoma, Renal Cell Leiomyomatosis Neoplastic Syndromes, Hereditary Skin Neoplasms Uterine Neoplasms Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases |
Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Kidney Diseases Urologic Diseases Male Urogenital Diseases Leiomyoma Neoplasms, Muscle Tissue Neoplasms, Connective and Soft Tissue Genetic Diseases, Inborn Skin Diseases Genital Neoplasms, Female Uterine Diseases Genital Diseases, Female Genital Diseases Bevacizumab |