Clinical Trial: NCT04579224 - My Cancer Genome

NCT04579224

Description:

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.

Related Conditions:

Urothelial Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04579224

Trial Eligibility

Document

Title

Brief Title: Comparing the New Anti-cancer Drug Eribulin With or Without Chemotherapy Against the Usual Chemotherapy Alone in 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

Clinical Trial IDs

ORG STUDY ID: NCI-2020-07651
SECONDARY ID: NCI-2020-07651
SECONDARY ID: S1937
SECONDARY ID: S1937
SECONDARY ID: U10CA180888
NCT ID: NCT04579224

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

Interventions

Drug	Synonyms	Arms
Docetaxel	Docecad, RP56976, Taxotere, Taxotere Injection Concentrate	Arm I (standard of care chemotherapy)
Eribulin Mesylate	B1939 Mesylate, E7389, ER-086526, Halaven, Halichondrin B Analog	Arm II (eribulin)
Gemcitabine Hydrochloride	dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011	Arm I (standard of care chemotherapy)
Paclitaxel	Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat	Arm I (standard of care chemotherapy)

Purpose

Detailed Description

      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

Trial Arms

Name	Type	Description	Interventions
Arm I (standard of care chemotherapy)	Active Comparator	Patients receive 1 of the 3 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.	Docetaxel Gemcitabine Hydrochloride Paclitaxel
Arm II (eribulin)	Experimental	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.	Eribulin Mesylate
Arm III (eribulin, gemcitabine)	Experimental	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.	Eribulin Mesylate Gemcitabine Hydrochloride

Eligibility 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 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

        Exclusion Criteria:

          -  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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Overall survival
Time Frame:	From date of registration to date of death due to any cause, assessed up to 3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:	Progression free survival
Time Frame:	From date of registration to date of first documentation of progression or symptomatic deterioration (as defined in above), or death due to any cause, assessed up to 3 years
Safety Issue:
Description:

Measure:	Overall response rate
Time Frame:	3 years
Safety Issue:
Description:

Measure:	Duration of response
Time Frame:	Date from initial documentation of PR or CR to progression or death from any cause, whichever comes first, assessed up to 3 years
Safety Issue:
Description:	Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

Measure:	Disease control rate
Time Frame:	Up to 3 years
Safety Issue:
Description:	Percentage of patients achieving at least a stable disease as best response on imaging using RECIST 1.1 criteria during treatment.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	National Cancer Institute (NCI)

Last Updated

August 25, 2021

Clinical Trials /

Comparing the New Anti-cancer Drug Eribulin With or Without Chemotherapy Against the Usual Chemotherapy Alone in Metastatic Urothelial Cancer