Comparing the New Anti-cancer Drug Eribulin With Chemotherapy Against the Usual Chemotherapy Alone in Metastatic Urothelial Cancer
Purpose
This phase III trial compares the usual chemotherapy treatment to eribulin plus gemcitabine in treating patients with urothelial cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as eribulin, gemcitabine, docetaxel, paclitaxel, and sacituzumab govitecan 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. This trial aims to see whether adding eribulin to standard of care chemotherapy may work better in treating patients with metastatic urothelial cancer.
Conditions
- Metastatic Bladder Urothelial Carcinoma
- Metastatic Renal Pelvis Urothelial Carcinoma
- Metastatic Ureter Urothelial Carcinoma
- Metastatic Urethral Urothelial Carcinoma
- Metastatic Urothelial Carcinoma
- Refractory Bladder Urothelial Carcinoma
- Refractory Renal Pelvis Urothelial Carcinoma
- Refractory Ureter Urothelial Carcinoma
- Refractory Urethral Urothelial Carcinoma
- Refractory Urothelial Carcinoma
- Stage IV Bladder Cancer AJCC v8
- Stage IV Renal Pelvis and Ureter Cancer AJCC v8
- Stage IV Renal Pelvis Cancer AJCC v8
- Stage IV Ureter Cancer AJCC v8
- Stage IV Urethral Cancer AJCC v8
- Stage IVA Bladder Cancer AJCC v8
- Stage IVB Bladder Cancer AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Participant must have predominant histologically and cytologically proven urothelial
carcinoma in a metastatic site
- Participant must have evidence of metastatic urothelial carcinoma based on CT or MRI
within 28 days prior to registration
- Participant must have had progression of disease following prior therapy at the
discretion of the treating investigator
- Participants must not require immediate central nervous system (CNS)-specific
treatment, in the opinion of the treating investigator if they have active brain
metastases (defined as new or progressive brain metastases) or leptomeningeal
disease
- Participant must have had prior systemic therapy in metastatic setting that:
- Included enfortumab vedotin
- Included a PD1/PDL1 antibody
- NOTE: Under the discretion of the treating physician, participants who are
not candidates for PD1/PDL1 antibody systemic therapy are allowed
- Any systemic therapy provided in adjuvant, neoadjuvant, or chemoradiation
settings for urothelial carcinoma can be considered to be in metastatic
setting, if the last day of treatment was within 12 months prior to the
diagnosis of metastatic disease
- Participant must have completed any planned surgery or radiation therapy prior to
registration
- Participant must not have unresolved toxicities from prior surgeries or radiation
therapy > grade 1 at the time of registration
- Participant must be ≥ 18 years of age
- Participant must have Zubrod performance status 0-2
- Participant must have history and physical examination within 28 days prior to
registration
- Participant must have complete blood count (CBC), complete metabolic panel including
liver function tests, and lactate dehydrogenase (LDH) obtained with 28 days prior to
registration
- Participant must have adequate kidney function as evidenced by measured or
calculated creatinine clearance >= 20 mL/min within 28 days prior to registration
- Participant must have adequate hepatic function documented by either aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x institutional upper
limit of normal (IULN) within 28 days prior to registration. If both AST and ALT are
performed, both must be =< 3 x IULN. For participants with liver metastases, AST or
ALT must be =< 5 x IULN
- Participant must be on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test and within 6 months prior to registration
if they are known to have human immunodeficiency virus (HIV)-infection
- Participants must have undetectable hepatitis B virus (HBV) viral load within 28
days prior to registration if participant has known chronic hepatitis B virus (HBV)
infection
- Participants with a known history of hepatitis C virus (HCV) infection must have an
undetectable HCV viral load within 28 days prior to registration
- Participants may have a prior or concurrent malignancy provided the natural history
or treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen per the opinion of the treating
investigator
- Participants must not be planning to take strong or moderate CYP3A or CYP2C8
inhibitors or inducers if randomized to Arm 1 and standard of care (SOC) regimen
chosen is paclitaxel or docetaxel. Participants receiving strong or moderate CYP3A-
or CYP2C8 inducers must discontinue use at least 2 weeks prior to randomization
- Participant must not have a known history of corrected QT (QTc) prolongation
- Participants must not be pregnant or nursing due to the risk of harm to a fetus or
nursing infant. Women and men of reproductive potential must have agreed to use an
effective contraceptive method for the course of the study and 6 months (females) or
3.5 months (males) after the last dose. A woman is considered to be of "reproductive
potential" if she has had menses at any time in the preceding 12 consecutive months.
In addition to routine contraceptive methods, "effective contraception" also
includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) defined as a hysterectomy, bilateral
oophorectomy or bilateral tubal ligation. However, if at any point a previously
celibate participant chooses to become heterosexually active during the time period
for use of contraceptive measures outlined in the protocol, he/she is responsible
for beginning contraceptive measures
- Participants must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and federal
guidelines
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (standard of care chemotherapy) |
Patients receive 1 of the 4 standard of care chemotherapy regimens based on treating investigator's choice: Choice A: Patients receive docetaxel IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Choice B: Patients receive gemcitabine IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Choice C: Patients receive paclitaxel IV on days 1, 8, and 15. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Choice D: Patients receive sacituzumab govitecan IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI and bone scan throughout the trial. Patients also undergo blood and urine sample collection on the trial. |
|
|
Experimental Arm II (eribulin) |
Patients receive eribulin IV over 2-5 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI and bone scan throughout the trial. Patients also undergo blood and urine sample collection on the trial. (CLOSED TO ACCRUAL) |
|
|
Experimental Arm III (eribulin, gemcitabine) |
Patients receive eribulin IV over 2-5 minutes and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI and bone scan throughout the trial. Patients also undergo blood and urine sample collection on the trial. |
|
Recruiting Locations
Kansas City, Kansas 66160
Westwood, Kansas 66205
Kansas City, Missouri 64154
North Kansas City, Missouri 64116
Lee's Summit, Missouri 64064
Overland Park, Kansas 66210
Overland Park, Kansas 66211
Topeka, Kansas 66606
Site Public Contact
785-295-8000
More Details
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Study Contact
Detailed Description
PRIMARY OBJECTIVES: I. To compare overall survival in participants with metastatic urothelial carcinoma (mUC) who are randomized to standard treatment versus eribulin plus gemcitabine hydrochloride (gemcitabine). SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS) in the standard treatment arm to the experimental treatment arm in this population. II. To compare Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 overall response rate (ORR), both confirmed and unconfirmed, complete and partial responses (CR and PR), in the standard treatment arm to the experimental treatment arm in the subset of participants with measurable disease in this population. III. To compare duration of response (DOR) in the standard treatment arm to the experimental treatment arm in the subset of participants with measurable disease in this population. IV. To compare disease control rate (DCR) in the standard treatment arm to the experimental treatment arm in the subset of participants with measurable disease in this population. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive 1 of the 4 standard of care chemotherapy regimens based on treating investigator's choice: Choice A: Patients receive docetaxel intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Choice B: Patients receive gemcitabine IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Choice C: Patients receive paclitaxel IV on days 1, 8, and 15. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Choice D: Patients receive sacituzumab govitecan IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive eribulin IV over 2-5 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL) ARM III: Patients receive eribulin IV over 2-5 minutes and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients undergo computed tomography (CT), magnetic resonance imaging (MRI) and bone scan throughout the trial. Patients also undergo blood and urine sample collection on the trial. After completion of study treatment, patients are followed up every 6 months for 2 years from the date of registration, then every 12 months until death or 3 years from the date of registration