Transitional Cell CarcinomaPhase 2NCT01215136
First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
A Phase 2 study testing Everolimus and Paclitaxel in people with Transitional Cell Carcinoma and Bladder Carcinoma, run by Matthew Galsky at 11 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transitional Cell Carcinoma, Bladder Carcinoma, Urothelial Carcinoma
- What is being tested?
- Everolimus and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 11 sitesUnited States
- Study dates
- Dec 2010to 24 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, 35294
Cancer Care Center of Southern Indiana
Bloomington, Indiana, 47403
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, 60611
University of Texas Medical Branch
Galveston, Texas, 77555
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, 46219
Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, 10029
Virginia Oncology Associates
Norfolk, Virginia, 23502
Nebraska Cancer Specialists
Omaha, Nebraska, 68114
Metro Health Cancer Care
Wyoming, Michigan, 49519
About this study
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
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.
Read the 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.
- Being tested
- Everolimus, Paclitaxel
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
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.
EverolimusDrug
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.
PaclitaxelDrug
Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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%) Receives: 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%) Receives: Drug: Everolimus; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (3)
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.
Measured: 5 months
Progression Free Survival
To determine median progression free survival per RECIST 1.1, per cohort.
Measured: 4 months
Overall Survival
To determine median overall survival at 1-year from the initiation of treatment.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2010 (estimated)
- Study startDec 2010
- Primary completion24 Apr 2017
- Study completion24 Apr 2018
Why it stopped: Lack of Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transitional Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matthew Galsky
- Sponsor type
- University, hospital or other
- Collaborators
- Hoosier Cancer Research Network, Novartis Pharmaceuticals
- Responsible party
- Sponsor-investigator, Matthew Galsky, Hoosier Cancer Research Network
- Investigators
- Matthew Galsky, M.D., Study chair, Hoosier Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01215136
- Sponsor's protocol ID
- HCRN GU10-147
- Status last verified
- Nov 2023
- First submitted
- 4 Oct 2010
- Last updated
- 24 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35438782
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01215136
- Acronym / sponsor ID
- HCRN GU10-147
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Accrual
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Matthew GalskyUniversity, hospital or other
- Collaborators
- Hoosier Cancer Research Network, Novartis Pharmaceuticals
- Study start
- Dec 2010
- Primary completion
- 24 Apr 2017 (actual)
- Study completion
- 24 Apr 2018 (actual)
- First posted
- 6 Oct 2010 (estimated)
- Results
- Posted 24 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Active comparator | Drug: EverolimusSingle-agent everolimus (enrollment limited to patients with patients with creatinine clearance < 60 ml/min AND Karnofsky performance status of 60-70%) |
| Cohort 2 | Active comparator | Drug: Everolimus, Drug: PaclitaxelEverolimus plus paclitaxel (enrollment limited to patients with creatinine clearance < 60 ml/min OR Karnofsky performance status of 60-70%) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus10 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 | Cohort 1 |
| Everolimus10 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 | Cohort 2 |
| PaclitaxelPaclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle. | Drug | Cohort 2 |
Primary outcome
Response Rate of Single-Agent Everolimus and Everolimus + Paclitaxel
Time frame: 4 months
To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.
3 secondary outcomes
Number of Adverse Events as a Measure of Safety and Tolerability
Time frame: 5 months
Progression Free Survival
Time frame: 4 months
Overall Survival
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35438782Jun 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.
- Hoosier Oncology Group HomepageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Galsky, M.D. study chair
Hoosier Cancer Research Network
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and Paclitaxel in people with Transitional Cell Carcinoma and Bladder Carcinoma, run by Matthew Galsky at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate of Single-Agent Everolimus and Everolimus + Paclitaxel (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01215136, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.