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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Hoosier Cancer Research Network
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT01215136
First received: October 4, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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 Oncology Group 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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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 ClinicalTrials.gov identifier: NCT01215136

Contacts
Contact: Matthew Galsky, M.D. matthew.galsky@mssm.edu
Contact: Cynthia Burkhardt, R.N. 317.921.2050 cyburkha@iupui.edu

Locations
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    gsonpavde@uabmc.edu   
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    t-kuzel@northwestern.edu   
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    calbany@iupui.edu   
Contact: Kerry Bridges    317.274.2552    kdbridge@iupui.edu   
IU Health Central Indiana Cancer Centers Recruiting
Indianapolis, Indiana, United States, 46219
Contact: Harold Longe, M.D.    317-356-2422    hlonge@iuhealth.org   
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    rhauke@nebraskacancer.com   
Contact: Kim Bland, R.N.    402-354-5144    kbland@mnhs.org   
United States, New York
Tisch Cancer Institute at Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Matthew Galsky, M.D.    212-241-8214    matthew.galsky@mssm.edu   
United States, South Carolina
MUSC Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Contact: Harry Drabkin, M.D.       drabkin@musc.edu   
Contact: Alan Brisendine    843-792-9007    brisend@musc.edu   
United States, Texas
University of Texas Medical Branch Not yet recruiting
Galveston, Texas, United States, 77555
Contact: Bagi Jana, M.D.    409-772-1164    brjana@utmb.edu   
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Mark Fleming, M.D.    757-213-5813    mark.fleming@usoncology.com   
Contact: Wendi Gobhart    757.213.5813    wendi.gobhart@usoncology.com   
Sponsors and Collaborators
Hoosier Cancer Research Network
Novartis Pharmaceuticals
Investigators
Study Chair: Matthew Galsky, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01215136     History of Changes
Other Study ID Numbers: HOG GU10-147
Study First Received: October 4, 2010
Last Updated: April 14, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Carcinoma
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Paclitaxel
Sirolimus
Everolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on September 22, 2014