A Phase III Randomized Trial of Eribulin (NSC #707389) With Gemcitabine Versus Standard of Care (Physician's Choice) for Treatment of Metastatic Urothelial Carcinoma Refractory to, or Ineligible for, Anti PD1/PDL1 Therapy
A Phase III Randomized Trial of Eribulin (NSC #707389) With Gemcitabine Versus Standard of Care (Physician's Choice) for Treatment of Metastatic Urothelial Carcinoma Refractory to, or Ineligible for, Anti PD1/PDL1 Therapy
This phase III trial compares the usual chemotherapy treatment to eribulin plus gemcitabine in treating patients with urothelial cancer that has spread from where it first started (primary site) 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.
PRIMARY OBJECTIVE:
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 of each cycle. 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 of each cycle. 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 of each cycle. 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 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. (EFFECTIVE NOVEMBER 18, 2024: sacituzumab govitecan is no longer included in Arm 1 for newly enrolled patients).
ARM II: Patients receive eribulin IV over 2-5 minutes on days 1 and 8 of each cycle. 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 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All patients undergo computed tomography (CT), magnetic resonance imaging (MRI) throughout the trial and may undergo bone scan at the discretion of the treating physician. 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
Inclusion Criteria:
Participant must have predominant histologically or 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
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 within 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 offered the opportunity to participate in specimen banking as outlined
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
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Irvine, California 92612, United States
Sacramento, California 95817, United States
Brighton, Michigan 48114, United States
Brownstown, Michigan 48183, United States
Chelsea, Michigan 48118, United States
East China Township, Michigan 48054, United States
Grand Rapids, Michigan 49503, United States
West Branch, Michigan 48661, United States
Ypsilanti, Michigan 48197, United States
North Kansas City, Missouri 64116, United States
East Syracuse, New York 13057, United States
Harrisburg, Pennsylvania 17109, United States
Mechanicsburg, Pennsylvania 17050, United States
Houston, Texas 77030, United States
Silverdale, Washington 98383, United States
Yakima, Washington 98902, United States
Stevens Point, Wisconsin 54482, United States
Sturgeon Bay, Wisconsin 54235-1495, United States