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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Transitional Cell Carcinoma, Bladder Carcinoma, Urothelial Carcinoma

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.

Outcome Time Frame:

4 months

Safety Issue:

No

Principal Investigator

Matthew Galsky, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Hoosier Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

HOG GU10-147

NCT ID:

NCT01215136

Start Date:

December 2010

Completion Date:

December 2013

Related Keywords:

  • Transitional Cell Carcinoma
  • Bladder Carcinoma
  • Urothelial Carcinoma
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Transitional Cell

Name

Location

Virginia Oncology AssociatesNewport News, Virginia  23606
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Methodist Cancer CenterOmaha, Nebraska  68114
Northwestern University Feinberg School of MedicineChicago, Illinois  60611
Cancer Care Center Of Southern IndianaBloomington, Indiana  47403
MUSC Hollings Cancer CenterCharleston, South Carolina  29425
Northwestern University, Robert H. Lurie Comprehensive Cancer CenterChicago, Illinois  60611
IU Health Central Indiana Cancer CentersIndianapolis, Indiana  46219
Metro Health Cancer CareWyoming, Michigan  49519
Tisch Cancer Institute at Mount Sinai Medical CenterNew York, New York  10029
University of Alabama Hematology Oncology Clinic at Medical WestBirmingham, Alabama  35294