Brief Title
First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
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
Brief 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Response Rate
Secondary Outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Condition
Transitional Cell Carcinoma
Intervention
Everolimus
Study Arms / Comparison Groups
Cohort 1
Description: Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance < 60 ml/min AND Karnofsky performance status of 60-70%)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
36
Start Date
December 2010
Completion Date
April 24, 2018
Primary Completion Date
April 24, 2017
Eligibility 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Matthew Galsky, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01215136
Organization ID
HCRN GU10-147
Responsible Party
Sponsor-Investigator
Study Sponsor
Matthew Galsky
Collaborators
Hoosier Cancer Research Network
Study Sponsor
Matthew Galsky, M.D., Study Chair, Hoosier Cancer Research Network
Verification Date
October 2019