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First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01215136
Recruitment Status : Active, not recruiting
First Posted : October 6, 2010
Last Update Posted : December 22, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this trial is to explore the activity and safety of everolimus +/- paclitaxel as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma.

Condition or disease Intervention/treatment Phase
Transitional Cell Carcinoma Bladder Carcinoma Urothelial Carcinoma Drug: Everolimus Drug: Paclitaxel Phase 2

Detailed Description:

OUTLINE: This is a multi-center study

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


  • 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


  • Bilirubin ≤ 1.5 x ULN
  • Aminotransferases (AST and ALT) ≤ 2.5 x ULN (unless liver metastases, then ≤ 5 x ULN)


  • Calculated creatinine clearance of < 60 using the Cockcroft-Gault formula


  • 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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Everolimus or Everolimus Plus Paclitaxel as First-line Therapy in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma: Hoosier Cancer Research Network GU10-147
Study Start Date : December 2010
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : April 2018

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Cohort 1
Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance < 60 ml/min AND Karnofsky performance status of 60-70%)
Drug: 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.
Active Comparator: Cohort 2
Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance < 60 ml/min OR Karnofsky performance status of 60-70%)
Drug: 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.
Drug: Paclitaxel
Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.

Outcome Measures

Primary Outcome Measures :
  1. Response Rate [ Time Frame: 4 months ]
    To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.

Secondary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 4 months ]
    To determine the safety of everolimus and everolimus plus paclitaxel in this patient population.

  2. Progression Free Survival [ Time Frame: 4 months ]
    To determine progression free survival

  3. Survival - 1 year [ Time Frame: 12 months ]
    To determine survival at 1-year from the initiation of treatment.

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological or cytological proof of transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis (urothelial carcinoma). Histology may be mixed, but still requires a component of TCC.
  • 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 prior chemotherapy for metastatic disease. Prior chemotherapy in the neoadjuvant/adjuvant setting is allowed if completed at least 12 months prior to registration for protocol therapy.
  • 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.
Contacts and Locations

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): NCT01215136

United States, Alabama
University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, United States, 35294
United States, Illinois
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
United States, Indiana
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States, 47403
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46219
United States, Michigan
Metro Health Cancer Care
Wyoming, Michigan, United States, 49519
United States, Nebraska
Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68114
United States, New York
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States, 10029
United States, South Carolina
MUSC Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
Sponsors and Collaborators
Matthew Galsky
Hoosier Cancer Research Network
Novartis Pharmaceuticals
Study Chair: Matthew Galsky, M.D. Hoosier Cancer Research Network
More Information

Additional Information:
Responsible Party: Matthew Galsky, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01215136     History of Changes
Other Study ID Numbers: HCRN GU10-147
First Posted: October 6, 2010    Key Record Dates
Last Update Posted: December 22, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents