First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
Conditions
Transitional Cell Carcinoma - Bladder Carcinoma - Urothelial Carcinoma
Conditions: official terms
Carcinoma - Carcinoma, Transitional Cell - Urinary Bladder Neoplasms
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Everolimus Type: Drug
Name: Everolimus Type: Drug
Name: Paclitaxel Type: Drug
Overall Status
Recruiting
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.
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

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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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.
Locations
University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, United States
Status: Recruiting
Contact: Guru Sonpavde, M.D. - 205-934-9999 - gsonpavde@uabmc.edu
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States
Status: Recruiting
Contact: Timothy Kuzel, M.D. - 312-695-0990 - t-kuzel@northwestern.edu
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States
Status: Withdrawn
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Status: Recruiting
Contact: Costantine Albany, M.D. - 317-278-1711 - calbany@iupui.edu
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Status: Recruiting
Contact: Harold Longe, M.D. - 317-356-2422 - hlonge@iuhealth.org
Metro Health Cancer Care
Wyoming, Michigan, United States
Status: Withdrawn
Nebraska Cancer Specialists
Omaha, Nebraska, United States
Status: Recruiting
Contact: Ralph Hauke, M.D. - 402-354-8124 - rhauke@nebraskacancer.com
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States
Status: Recruiting
Contact: Matthew Galsky, M.D. - 212-241-8214 - matthew.galsky@mssm.edu
MUSC Hollings Cancer Center
Charleston, South Carolina, United States
Status: Recruiting
Contact: Harry Drabkin, M.D. - drabkin@musc.edu
University of Texas Medical Branch
Galveston, Texas, United States
Status: Recruiting
Contact: Bagi Jana, M.D. - 409-772-1164 - brjana@utmb.edu
Virginia Oncology Associates
Norfolk, Virginia, United States
Status: Recruiting
Contact: Mark Fleming, M.D. - 757-213-5813 - mark.fleming@usoncology.com
Start Date
December 2010
Completion Date
December 2015
Sponsors
Matthew Galsky
Source
Hoosier Cancer Research Network
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page