Metastatic Ureter CarcinomaPhase 2NCT02178241
Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery
A Phase 2 study testing Eribulin Mesylate and Gemcitabine Hydrochloride in people with Metastatic Ureter Carcinoma and Metastatic Urethral Carcinoma, run by National Cancer Institute (NCI) at 18 sites in 2 countries.
Trial summary
This phase II trial studies how well gemcitabine hydrochloride and eribulin mesylate work in treating patients with bladder cancer that has spread to other places in the body or cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Ureter Carcinoma, Metastatic Urethral Carcinoma, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7
- What is being tested?
- Eribulin Mesylate and Gemcitabine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 11 Dec 2014to 11 Jul 2019
- Phase
- Phase 2
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
- Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment
- Patients must have histologically confirmed predominantly urothelial carcinoma of the bladder, ureter, or urethra
- Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- Patients must be ineligible for treatment with cisplatin, based on one of:
- Calculated creatinine clearance (CrCl) >= 30 and < 60 mL/min (Cockcroft-Gault)
- CTCAE grade (Gr) >= 2 hearing loss
Show all 18Show fewer
- CTCAE Gr >= 2 neuropathy
- Patients must not have received prior systemic therapy for their advanced cancer; prior intravesical therapy completed 4 weeks prior to enrollment and adjuvant/neoadjuvant chemotherapy completed more than 6 months prior to diagnosis of advanced disease are permitted
- Zubrod performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin < 1.5 times the upper limit of normal (x ULN) for the institution
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
- Creatinine clearance; calculated creatinine clearance (CrCl) >= 30 mL/min and < 60 mL/min (Cockroft-Gault) unless the patient qualified based on hearing loss or neuropathy
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of gemcitabine and eribulin administration
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients with a small cell component in their histology are excluded
- Patients who have had chemotherapy for the treatment of the advanced or unresectable urothelial cancer of the bladder are not eligible; patients who were previously treated for local disease must not have received radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have received neoadjuvant or adjuvant chemotherapy must have completed treatment at least 6 months prior to diagnosis of metastatic disease
- Patients who are receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine and eribulin
- Uncontrolled intercurrent illness including, but not limited to, a second cancer diagnosis within the past 5 years, or a cancer undergoing any treatment, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Show all 11Show fewer
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with eribulin and gemcitabine
- Human immunodeficiency virus (HIV)-positive patients with inadequate cluster of differentiation (CD)4 counts or those who are on combination antiretroviral therapy with strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) effects are ineligible for this trial
- Patients with baseline corrected QT (QTc) prolongation greater than grade 1 are excluded from this study; patients with grade 1 QTc elevation are eligible but must be monitored with electrocardiogram (ECG) (EKG) exams, for the first 3 cycles of treatment; eribulin time to maximum concentration (Cmax) after infusion is about 10 minutes, and half life is 40 minutes; ECG (EKG) should be performed between 10 to 40 minutes after eribulin administration (on day 1 and day 8 of treatment); continued ECG (EKG) monitoring beyond cycle 3 can be done at the discretion of the treating physician
- Patients with congenital long QT syndrome are excluded from this study
- Other medications known to prolong QT interval should be discontinued and if not possible, patient is excluded from this study
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States17 sites
University of Colorado Hospital
Aurora, Colorado, 80045
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Case Western Reserve University
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
University of Texas M D Anderson Cancer Center P2C
Houston, Texas, 77030
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
Keck Medical Center of USC Pasadena
Pasadena, California, 91105
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Mayo Clinic Cancer Center P2C
Rochester, Minnesota, 55905
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Moffitt Cancer Center P2C
Tampa, Florida, 33612
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Canada1 site
University Health Network Princess Margaret Cancer Center P2C
Toronto, Ontario, M5G 2M9
About this study
Official title: Phase II Trial of Gemcitabine-Eribulin (GE) in Cisplatin Ineligible Patients With Advanced or Unresectable Urothelial Carcinoma of the Bladder
This phase II trial studies how well gemcitabine hydrochloride and eribulin mesylate work in treating patients with bladder cancer that has spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the objective response rate of gemcitabine (gemcitabine hydrochloride)-eribulin (eribulin mesylate) (GE) when given to cisplatin ineligible patients with advanced or unresectable urothelial carcinoma who have not received any prior chemotherapy for the advanced disease.
SECONDARY OBJECTIVES:
- To estimate the median progression-free survival (PFS). II. To summarize the toxicity profile (using Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 criteria) of the GE regimen in these patients.
OUTLINE:
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 36 months.
- Conditions
- Metastatic Ureter Carcinoma, Metastatic Urethral Carcinoma, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Ureter Cancer AJCC v7, Stage III Urethral Cancer AJCC v7, Stage IV Bladder Urothelial Carcinoma AJCC v7
- Being tested
- Eribulin Mesylate, Gemcitabine Hydrochloride
- Medical subject headings
- Ureteral Neoplasms, Urethral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eribulin MesylateDrug
Also called B1939 Mesylate, E7389, ER-086526, Halaven
Given IV
Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (eribulin mesylate and gemcitabine hydrochloride) | Experimental | Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Eribulin Mesylate; Drug: Gemcitabine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Observed Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Observed Overall Response Rate = Number of patients who experienced a confirmed CR or PR divided by the number of eligible patients who began treatment.
Measured: Up to 36 months
Secondary outcomes (3)
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From the start until progression, death, or the start of another treatment, assessed up to 12 months
Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
Measured: From start of treatment until death from any cause ,up to 36 months
Incidence of Adverse Events.
Toxicities that Occurred in 10% or More of Patients or At Least Once as a Grade 3+ Adverse Event (excluding those toxicities classified as "unrelated" or "unlikely related" to study drugs). Toxicities graded using CTCAEv4 criteria.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2014 (estimated)
- Study start11 Dec 2014
- Primary completion18 Mar 2019
- Study completion11 Jul 2019
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 Metastatic Ureter CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sarmad Sadeghi, Principal investigator, City of Hope Comprehensive Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02178241
- Sponsor's protocol ID
- NCI-2014-01294
- Other IDs
- NCI-2014-01294, P9653_A02PAMDREVW01, PHII-130, 9653, 9653, N01CM00038, P30CA093373
- Status last verified
- Nov 2019
- First submitted
- 26 Jun 2014
- Last updated
- 16 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sadeghi S, Groshen SG, Tsao-Wei DD, Parikh R, Mortazavi A, Dorff TB, Kefauver C, Hoimes C, Doyle L, Quinn DI, Newman E, Lara PN Jr. Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653). J Clin Oncol. 2019 Oct 10;37(29):2682-2688. doi: 10.1200/JCO.19.00861. Epub 2019 Aug 7.
PubMed 31390274