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

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ClinicalTrials.gov Identifier: NCT04579224
Recruitment Status : Not yet recruiting
First Posted : October 8, 2020
Last Update Posted : February 15, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
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 Drug: Docetaxel Drug: Eribulin Mesylate Drug: Gemcitabine Hydrochloride Drug: Paclitaxel Phase 3

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 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 465 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 13, 2021
Estimated Primary Completion Date : August 15, 2027
Estimated Study Completion Date : August 15, 2027


Arm Intervention/treatment
Active Comparator: Arm I (standard of care chemotherapy)
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.
Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • FF 10832
  • FF-10832
  • FF10832
  • Gemcitabine HCI
  • Gemzar
  • LY-188011
  • LY188011

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

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.
Drug: Eribulin Mesylate
Given IV
Other Names:
  • B1939 Mesylate
  • E7389
  • ER-086526
  • Halaven
  • Halichondrin B Analog

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.
Drug: Eribulin Mesylate
Given IV
Other Names:
  • B1939 Mesylate
  • E7389
  • ER-086526
  • Halaven
  • Halichondrin B Analog

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • FF 10832
  • FF-10832
  • FF10832
  • Gemcitabine HCI
  • Gemzar
  • LY-188011
  • LY188011




Primary Outcome Measures :
  1. Overall survival [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. Overall response rate [ Time Frame: 3 years ]
  3. 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 ]
  4. Disease control rate [ Time Frame: Up to 3 years ]
    Percentage of patients achieving at least a stable disease as best response on imaging using Response Evaluation Criteria in Solid Tumors 1.1 criteria during treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have predominant and histologically/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 treatment for metastatic urothelial carcinoma with either a platinum-based chemotherapy regimen, systemic PD1/PDL1 immunotherapy, antibody conjugate, or enfortumab. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04579224


Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sarmad Sadeghi Southwest Oncology Group
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04579224    
Other Study ID Numbers: NCI-2020-07651
NCI-2020-07651 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1937 ( Other Identifier: SWOG )
S1937 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: February 15, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urethral Neoplasms
Ureteral Neoplasms
Pelvic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Ureteral Diseases
Gemcitabine
Paclitaxel
Docetaxel
Halichondrin B
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents