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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Hoosier Cancer Research Network
Hoosier Cancer Research Network
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Matthew Galsky, Hoosier Cancer Research Network Identifier:
First received: October 4, 2010
Last updated: March 13, 2015
Last verified: March 2015

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 Intervention Phase
Transitional Cell Carcinoma
Bladder Carcinoma
Urothelial Carcinoma
Drug: Everolimus
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.

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

  • Progression Free Survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    To determine progression free survival

  • Survival - 1 year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine survival at 1-year from the initiation of treatment.

Estimated Enrollment: 68
Study Start Date: December 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01215136

Contact: Matthew Galsky, M.D.
Contact: Lauren Wiehl 317.634.5842 ext 38

United States, Alabama
University of Alabama Hematology Oncology Clinic at Medical West Recruiting
Birmingham, Alabama, United States, 35294
Contact: Guru Sonpavde, M.D.    205-934-9999   
United States, Illinois
Northwestern University, Robert H. Lurie Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60611
Contact: Timothy Kuzel, M.D.    312-695-0990   
United States, Indiana
Cancer Care Center of Southern Indiana Withdrawn
Bloomington, Indiana, United States, 47403
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Costantine Albany, M.D.    317-278-1711   
Contact: Kerry Bridges    317.274.2552   
IU Health Central Indiana Cancer Centers Recruiting
Indianapolis, Indiana, United States, 46219
Contact: Harold Longe, M.D.    317-356-2422   
United States, Michigan
Metro Health Cancer Care Withdrawn
Wyoming, Michigan, United States, 49519
United States, Nebraska
Nebraska Cancer Specialists Recruiting
Omaha, Nebraska, United States, 68114
Contact: Ralph Hauke, M.D.    402-354-8124   
Contact: Kim Bland, R.N.    402-354-5144   
United States, New York
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Matthew Galsky, M.D.    212-241-8214   
United States, South Carolina
MUSC Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Contact: Harry Drabkin, M.D.   
Contact: Alan Brisendine    843-792-9007   
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555
Contact: Bagi Jana, M.D.    409-772-1164   
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Mark Fleming, M.D.    757-213-5813   
Contact: Wendi Gobhart    757.213.5813   
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:
No publications provided

Responsible Party: Matthew Galsky, Sponsor-Investigator, Hoosier Cancer Research Network Identifier: NCT01215136     History of Changes
Other Study ID Numbers: HCRN GU10-147
Study First Received: October 4, 2010
Last Updated: March 13, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators processed this record on March 25, 2015