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

Urothelial Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01215136
• Other study ID #: HCRN GU10-147
• Status: Terminated
• Phase: Phase 2
• Start date: December 2010
• Est. completion date: April 24, 2018

Study information

• Verified date: November 2023
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 36
• Est. completion date: April 24, 2018
• Est. primary completion date: April 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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.
• 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.
• Paclitaxel
Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.

Locations

Country	Name	City	State
United States	University of Alabama Hematology Oncology Clinic at Medical West	Birmingham	Alabama
United States	Cancer Care Center of Southern Indiana	Bloomington	Indiana
United States	MUSC Hollings Cancer Center	Charleston	South Carolina
United States	Northwestern University, Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Metro Health Cancer Care	Wyoming	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Matthew Galsky	Hoosier Cancer Research Network, Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate of Single-Agent Everolimus and Everolimus + Paclitaxel	To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.	4 months
Secondary	Number of Adverse Events as a Measure of Safety and Tolerability	To determine the safety of everolimus and everolimus plus paclitaxel in this patient population. A summary with the count of events per grade is provided.	5 months
Secondary	Progression Free Survival	To determine median progression free survival per RECIST 1.1, per cohort.	4 months
Secondary	Overall Survival	To determine median overall survival at 1-year from the initiation of treatment.	12 months

External Links

•   Hoosier Oncology Group Homepage