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BRIEF TITLE: 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

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


  • Org Study ID: NCI-2020-07651
  • Secondary ID: NCI-2020-07651,S1937,S1937,U10CA180888
  • NCT ID: NCT04579224
  • NCT Alias:
  • Sponsor: National Cancer Institute (NCI) - NIH
  • Source: 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.

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

Overal Status Start Date Phase Study Type
Recruiting February 16, 2021 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Overall survival

Primary Outcome 1 - Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years

Condition:

  • 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

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 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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Sarmad Sadeghi

Role: Principal Investigator

Affiliation: Southwest Oncology Group

Locations

Facility Status Contact
Mary Greeley Medical Center
Ames, Iowa 50010
United States
Recruiting Site Public Contact
515-956-4132
McFarland Clinic PC - Ames
Ames, Iowa 50010
United States
Recruiting Site Public Contact
515-239-4734
ksoder@mcfarlandclinic.com
McFarland Clinic PC-Boone
Boone, Iowa 50036
United States
Recruiting Site Public Contact
515-956-4132
McFarland Clinic PC-Trinity Cancer Center
Fort Dodge, Iowa 50501
United States
Recruiting Site Public Contact
515-956-4132
McFarland Clinic PC-Jefferson
Jefferson, Iowa 50129
United States
Recruiting Site Public Contact
515-956-4132
McFarland Clinic PC-Marshalltown
Marshalltown, Iowa 50158
United States
Recruiting Site Public Contact
515-956-4132