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

October 4, 2010
April 14, 2014
December 2010
December 2015   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01215136 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
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

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.

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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Transitional Cell Carcinoma
  • Bladder Carcinoma
  • Urothelial Carcinoma
  • 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.
  • 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%)
    Intervention: Drug: Everolimus
  • Active Comparator: Cohort 2
    Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance < 60 ml/min OR Karnofsky performance status of 60-70%)
    Interventions:
    • Drug: Everolimus
    • Drug: Paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
68
December 2015
December 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Matthew Galsky, M.D. matthew.galsky@mssm.edu
Contact: Cynthia Burkhardt, R.N. 317.921.2050 cyburkha@iupui.edu
United States
 
NCT01215136
HOG GU10-147
Yes
Hoosier Cancer Research Network
Hoosier Cancer Research Network
Novartis Pharmaceuticals
Study Chair: Matthew Galsky, M.D. Hoosier Cancer Research Network
Hoosier Cancer Research Network
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP