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

NCT01215136 | Terminated Phase 2 Results DMC

• 1 other identifier: HCRN GU10-147
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 11

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.

Conditions

Transitional Cell Carcinoma; Bladder Carcinoma; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Adverse Events as a Measure of Safety and Tolerability

  5 months

• Progression Free Survival

  4 months

• Overall Survival

  12 months

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%)

Drug: Everolimus

Cohort 2

ACTIVE COMPARATOR

Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%)

Drug: Everolimus; Drug: Paclitaxel

Interventions

Everolimus DRUG

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.

Cohort 1

Paclitaxel DRUG

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

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Matthew Galsky: lead
• Hoosier Cancer Research Network: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (11)

University of Alabama Hematology Oncology Clinic at Medical West

Birmingham, Alabama, 35294, United States

Location

Northwestern University, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

Cancer Care Center of Southern Indiana

Bloomington, Indiana, 47403, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, 46219, United States

Location

Metro Health Cancer Care

Wyoming, Michigan, 49519, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68114, United States

Location

Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, 10029, United States

Location

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Related Publications (1)

• Jun T, Hahn NM, Sonpavde G, Albany C, MacVicar GR, Hauke R, Fleming M, Gourdin T, Jana B, Oh WK, Taik P, Wang H, Varadarajan AR, Uzilov A, Galsky MD. Phase II Clinical and Translational Study of Everolimus +/- Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma. Oncologist. 2022 Jun 8;27(6):432-e452. doi: 10.1093/oncolo/oyab075.

  PMID: 35438782 DERIVED

Related Links

• Hoosier Oncology Group Homepage

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

Everolimus; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Clinicaltrials.gov Results Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-643-5842

Study Officials

• Matthew Galsky, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 4, 2010
• First Posted: October 6, 2010
• Study Start: December 1, 2010
• Primary Completion: April 24, 2017
• Study Completion: April 24, 2018
• Last Updated: November 24, 2023
• Results First Posted: November 24, 2023

Record last verified: 2023-11

Locations

US (11)