First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
NCT ID: NCT01215136
Last Updated: 2023-11-24
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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TERMINATED
PHASE2
36 participants
INTERVENTIONAL
2010-12-31
2018-04-24
Brief Summary
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Detailed Description
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Patients will be enrolled into one of two parallel cohorts:
* Cohort 1: impaired renal function AND poor performance status (cycle length = 28 days). Everolimus 10 mg orally daily
* Cohort 2: impaired renal function OR poor performance status (cycle length = 28 days). Everolimus 10 mg orally daily + IV Paclitaxel 80 mg/m2 on D1, 8, 15
Restaging evaluations will be performed after every 2 cycles.
Treatment will continue until disease progression or unacceptable toxicity.
Karnofsky performance status 60-70%
Life Expectancy: Not specified
Hematopoietic:
* Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
* Hemoglobin (Hgb) ≥ 9 g/dL
* Platelets ≥ 100 K/mm3
* INR ≤ 1.5 (Anticoagulants are allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of Low molecular weight (LMW) heparin for at least 2 weeks prior to registration for protocol therapy).
* Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L
* Fasting triglycerides ≤ 2.5 x ULN.
* Fasting serum glucose \< 1.5 x ULN
Hepatic:
* Bilirubin ≤ 1.5 x ULN
* Aminotransferases (AST and ALT) ≤ 2.5 x ULN (unless liver metastases, then ≤ 5 x ULN)
Renal:
* Calculated creatinine clearance of \< 60 using the Cockcroft-Gault formula
Cardiovascular:
* No symptomatic congestive heart failure of New York heart Association Class III or IV.
* No unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 1
Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%)
Everolimus
10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.
Cohort 2
Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%)
Everolimus
10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.
Paclitaxel
Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Interventions
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Everolimus
10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.
Everolimus
10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.
Paclitaxel
Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Eligibility Criteria
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Inclusion Criteria
* Measurable disease according to RECIST and obtained by imaging within 30 days prior to registration for protocol therapy.
* Must be ineligible for cisplatin, based on the following, within 30 days prior to registration for protocol therapy.
* Prior radiation therapy is allowed to \< 25% of the bone marrow.
* Written informed consent and HIPAA authorization for release of personal health information.
* Age \> 18 years at the time of consent.
* Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
* Females of childbearing potential must have a negative pregnancy test within 7 days prior to prior to registration for protocol therapy.
* Females must not be breastfeeding.
Exclusion Criteria
* No active CNS metastases or leptomeningeal metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
* No prior malignancy is allowed except for adequately treated basal cell or adequately treated squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 7 prostate cancers (treated definitively with no evidence of PSA progression), or other cancer for which the patient has been disease-free for at least 5 years.
* No treatment with any anticancer therapy or investigational agent within 30 days prior to registration for protocol therapy.
* No known hypersensitivity to any protocol treatment.
* No prior treatment with mTOR inhibitor (sirolimus, temsirolimus, everolimus).
* No history of immunization with attenuated live vaccines within one week prior to registration for protocol therapy or during study period.
* No severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air.
* No uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN.
* No active (acute or chronic) or uncontrolled severe infections.
* No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
* No known history of HIV seropositivity.
* No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
* No active, bleeding diathesis.
* No history of major surgery (defined as requiring general anesthesia) or significant traumatic injury within 30 days prior to registration for protocol therapy.
18 Years
ALL
No
Sponsors
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Hoosier Cancer Research Network
OTHER
Novartis Pharmaceuticals
INDUSTRY
Matthew Galsky
OTHER
Responsible Party
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Matthew Galsky
Sponsor-Investigator
Principal Investigators
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Matthew Galsky, M.D.
Role: STUDY_CHAIR
Hoosier Cancer Research Network
Locations
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University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, United States
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Metro Health Cancer Care
Wyoming, Michigan, United States
Nebraska Cancer Specialists
Omaha, Nebraska, United States
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States
MUSC Hollings Cancer Center
Charleston, South Carolina, United States
University of Texas Medical Branch
Galveston, Texas, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
Countries
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References
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Jun T, Hahn NM, Sonpavde G, Albany C, MacVicar GR, Hauke R, Fleming M, Gourdin T, Jana B, Oh WK, Taik P, Wang H, Varadarajan AR, Uzilov A, Galsky MD. Phase II Clinical and Translational Study of Everolimus +/- Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma. Oncologist. 2022 Jun 8;27(6):432-e452. doi: 10.1093/oncolo/oyab075.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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Hoosier Oncology Group Homepage
Other Identifiers
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HCRN GU10-147
Identifier Type: -
Identifier Source: org_study_id