Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Davis
Dates
study started
estimated completion

Description

Summary

This phase III trial compares the usual chemotherapy treatment to eribulin alone and 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, and paclitaxel, 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.

Official Title

A Phase III Randomized Trial of Eribulin (NSC #707389) With or Without Gemcitabine Versus Standard of Care (Physician's Choice) for Treatment of Metastatic Urothelial Carcinoma Refractory to, or Ineligible for, Anti PD1/PDL1 Therapy

Details

PRIMARY OBJECTIVES: I. To compare overall survival (OS) in participants with metastatic urothelial carcinoma (mUC) who are randomized to standard treatment versus eribulin mesylate (eribulin) alone. II. To compare overall survival in participants with metastatic urothelial carcinoma (mUC) who are randomized to standard treatment versus eribulin plus gemcitabine hydrochloride (gemcitabine). III. To compare overall survival in participants with metastatic urothelial carcinoma (mUC) who are randomized to eribulin alone versus eribulin plus gemcitabine. SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS) in the standard treatment arm to the two experimental treatment arms 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 two experimental treatment arms 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 two experimental treatment arms 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 two experimental treatment arms 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 3 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. 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. 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. 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

Keywords

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 Carcinoma Urinary Bladder Neoplasms Carcinoma, Transitional Cell Urethral Neoplasms Ureteral Neoplasms Pelvic Neoplasms Gemcitabine Paclitaxel Docetaxel Halichondrin B Albumin-Bound Paclitaxel Eribulin Mesylate Gemcitabine Hydrochloride

Eligibility

You can join if…

Open to people ages 18 years and up

  • Participant must have predominant histologically and cytologically proven urothelial carcinoma in a metastatic site
  • Participant must have evidence of metastatic urothelial carcinoma based on computed tomography (CT) or magnetic resonance imaging (MRI) within 28 days prior to registration
  • Participant must have had progression of disease following prior therapy at the discretion of the treating investigator
  • Participant must have received previous systemic treatment for metastatic urothelial carcinoma with either a platinum-based chemotherapy regimen, systemic PD1/PDL1 immunotherapy, an antibody drug conjugate such as, enfortumab vedotin or sacituzumab govitecan (through standard of care or a clinical trial). There is no limit to the number of prior regimens patient may have received for urothelial carcinoma
  • If participant is a candidate for a platinum-based chemotherapy, then participant must have previously received a platinum-based chemotherapy
  • If participant is a candidate for immunotherapy, then participant must have previously received immunotherapy. If participant is not a candidate for immunotherapy, then participant either: (a) must have had prior anti PD1/PDL1 antibody therapy; OR (b) must have not been a candidate for anti PD1/PDL1 antibody therapy in the opinion of the treating physician
  • Participant is eligible if platinum based chemotherapy and/or anti PDL/PDL1 antibody therapy was provided in perioperative setting before or after radical cystectomy and if there is evidence of progression to metastatic disease within 12 months of the last dose of therapy. For instance, a patient treated with dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in neoadjuvant setting, then radical cystectomy followed by adjuvant pembrolizumab on AMBASSADOR trial will meet the requirement for prior/concurrent therapy if progression of disease occurs within 12 months of discontinuation of pembrolizumab
  • Participant must have received any planned surgery prior to registration
  • 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 >= 50 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 be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

You CAN'T join if...

  • 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 not have progressed within 3 months following last dose of gemcitabine
  • Participant must not have unresolved toxicities from prior surgeries or radiation therapy > grade 1 at the time of registration to registration
  • 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

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • USC Norris Oncology/Hematology-Newport Beach accepting new patients
    Newport Beach California 92663 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Cancer Institute (NCI)
ID
NCT04579224
Phase
Phase 3
Study Type
Interventional
Last Updated