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BRIEF TITLE: An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)

An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)


  • Org Study ID: 7465-CL-0301
  • Secondary ID:
  • NCT ID: NCT03474107
  • NCT Alias:
  • Sponsor: Astellas Pharma Global Development, Inc. - Industry
  • Source: Astellas Pharma Inc

Brief Summary

The purpose of this study is to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy. This study will also compare progression-free survival on study therapy (PFS1); the overall response rate (ORR) and the disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of participants treated with EV to participants treated with chemotherapy. In addition, this study will evaluate the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy and assess the safety and tolerability of EV, as well as, the quality of life (QOL) and Patient Reported Outcomes (PRO) parameters.

Detailed Description


Participants considered an adult according to local regulation at the time of obtaining
informed consent may participate in the study.

Overal Status Start Date Phase Study Type
Recruiting June 27, 2018 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Overall Survival (OS)

Primary Outcome 1 - Time Frame: Up to 36 months

Condition:

  • Ureteral Cancer
  • Urothelial Cancer
  • Bladder Cancer

Eligibility

Criteria:
Inclusion Criteria:

- Subject is legally an adult according to local regulation at the time of signing
informed consent.

- Subject has histologically or cytologically confirmed urothelial carcinoma (i.e.,
cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with urothelial
carcinoma (transitional cell) with squamous differentiation or mixed cell types are
eligible.

- Subject must have experienced radiographic progression or relapse during or after a
checkpoint inhibitor (CPI) (anti-programmed cell death protein 1 (PD1) or
anti-programmed death-ligand 1 (PD-L1)) for locally advanced or metastatic disease.
Subjects who discontinued CPI treatment due to toxicity are eligible provided that the
subjects have evidence of disease progression following discontinuation. The CPI need
not be the most recent therapy. Subjects for whom the most recent therapy has been a
non-CPI based regimen are eligible if the subjects have progressed/relapsed during or
after the subjects most recent therapy. Locally advanced disease must not be amenable
to resection with curative intent per the treating physician.

- Subject must have received a platinum containing regimen (cisplatin or carboplatin) in
the metastatic/locally advanced, neoadjuvant or adjuvant setting. If platinum was
administered in the adjuvant/neoadjuvant setting subject must have progressed within
12 months of completion.

- Subject has radiologically documented metastatic or locally advanced disease at
baseline.

- An archival tumor tissue sample should be available for submission to central
laboratory prior to study treatment. If an archival tumor tissue sample is not
available, a fresh tissue sample should be provided. If a fresh tissue sample cannot
be provided due to safety concerns, enrollment into the study must be discussed with
the medical monitor.

- Subject has ECOG PS of 0 or 1

- The subject has the following baseline laboratory data:

- absolute neutrophil count (ANC) ≥ 1500/mm3

- platelet count ≥ 100 × 109/L

- hemoglobin ≥ 9 g/dL

- serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for
subjects with Gilbert's disease

- creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards
or as measured by 24 hour urine collection (glomerular filtration rate [GFR] can
also be used instead of CrCl)

- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
or ≤ 3 x ULN for subjects with liver metastases

- Female subject must either:

- Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year
without any menses for which there is no other obvious pathological or
physiological cause) prior to screening, or documented surgically sterile (e.g.,
hysterectomy, bilateral salpingectomy, bilateral oophorectomy).

- Or, if of childbearing potential: Agree not to try to become pregnant during the
study and for at least 6 months after the final study drug administration, and
have a negative urine or serum pregnancy test within 7 days prior to Day 1
(Females with false positive results and documented verification of negative
pregnancy status are eligible for participation), and if heterosexually active,
agree to consistently use a condom plus 1 form of highly effective birth control
per locally accepted standards starting at screening and throughout the study
period and for at least 6 months after the final study administration.

- Female subject must agree not to breastfeed or donate ova starting at screening and
throughout the study period, and for at least 6 months after the final study drug
administration.

- A sexually active male subject with female partner(s) who is of childbearing potential
is eligible if:

- Agrees to use a male condom starting at screening and continue throughout the
study treatment and for at least 6 months after final study drug administration.
If the male subject has not had a vasectomy or is not sterile as defined below
the subjects female partner(s) is utilizing 1 form of highly effective birth
control per locally accepted standards starting at screening and continue
throughout study treatment and for at least 6 months after the male subject
receives final study drug administration.

- Male subject must not donate sperm starting at screening and throughout the study
period, and for at least 6 months after the final study drug administration.

- Male subject with a pregnant or breastfeeding partner(s) must agree to abstinence or
use a condom for the duration of the pregnancy or time partner is breastfeeding
throughout the study period and for at least 6 months after the final study drug
administration.

- Subject agrees not to participate in another interventional study while on treatment
in present study.

Exclusion Criteria:

- Subject has preexisting sensory or motor neuropathy Grade ≥ 2.

- Subject has active central nervous system (CNS) metastases. Subjects with treated CNS
metastases are permitted on study if all the following are true:

- CNS metastases have been clinically stable for at least 6 weeks prior to
screening

- If requiring steroid treatment for CNS metastases, the subject is on a stable
dose ≤ 20 mg/day of prednisone or equivalent for at least 2 weeks

- Baseline scans show no evidence of new or enlarged brain metastasis

- Subject does not have leptomeningeal disease

- Subject has ongoing clinically significant toxicity (Grade 2 or higher with the
exception of alopecia) associated with prior treatment (including systemic therapy,
radiotherapy or surgery). Subject with ≤ Grade 2 immunotherapy-related hypothyroidism
or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose
of hormone replacement therapy (if indicated). Subjects with ongoing ≥ Grade 3
immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with
ongoing immunotherapy related colitis, uveitis, or pneumonitis or subjects with other
immunotherapy related AEs requiring high doses of steroids (> 20 mg/day of prednisone
or equivalent) are excluded.

- Subject has prior treatment with EV or other monomethyl auristatin E (MMAE)-based
Antibody drug conjugates (ADCs).

- Subject has received prior chemotherapy for urothelial cancer with all available study
therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions
where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and
vinflunine in regions where vinflunine is an approved therapy).

- Subject has received more than 1 prior chemotherapy regimen for locally advanced or
metastatic urothelial cancer, including chemotherapy for adjuvant or neo-adjuvant
disease if recurrence occurred within 12 months of completing therapy. The
substitution of carboplatin for cisplatin does not constitute a new regimen provided
no new chemotherapeutic agents were added to the regimen.

- Subject has history of another malignancy within 3 years before the first dose of
study drug, or any evidence of residual disease from a previously diagnosed
malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated
with curative intent with no evidence of progression, low-risk or very low-risk (per
standard guidelines) localized prostate cancer under active surveillance/watchful
waiting without intent to treat, or carcinoma in situ of any type (if complete
resection was performed) are allowed.

- Subject is currently receiving systemic antimicrobial treatment for viral, bacterial,
or fungal infection at the time of first dose of EV. Routine antimicrobial prophylaxis
is permitted.

- Subject has known active Hepatitis B (e.g., hepatitis B surface antigen (HBsAg)
reactive) or active hepatitis C (e.g., hepatitis C virus (HCV) Ribonucleic Acid (RNA)
[qualitative] is detected).

- Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or
2).

- Subject has documented history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms
(including congestive heart failure) consistent with New York Heart Association Class
III-IV within 6 months prior to the first dose of study drug.

- Subject has radiotherapy or major surgery within 4 weeks prior to first dose of study
drug.

- Subject has had chemotherapy, biologics, investigational agents, and/or antitumor
treatment with immunotherapy that is not completed 2 weeks prior to first dose of
study drug.

- Subject has known hypersensitivity to EV or to any excipient contained in the drug
formulation of EV; OR subject has known hypersensitivity to biopharmaceuticals
produced in Chinese hamster ovary (CHO) cells.

- Subject has known hypersensitivity to the following: docetaxel or to any of the other
excipients listed in product label, including polysorbate 80, paclitaxel or to any of
the other excipients listed in product label, such as macrogolglycerol ricinoleate 35
(Ph.Eur.); and vinflunine or to any of the other excipients listed in product label
such as other vinca alkaloids (vinblastine,vincristine, vindesine, vinorelbine).

- Subject has known active keratitis or corneal ulcerations.

- Subject has other underlying medical condition that would impair the ability of the
subject to receive or tolerate the planned treatment and follow-up.

- History of uncontrolled diabetes mellitus within 3 months of the first dose of study
drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c between
7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not
otherwise explained.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Senior Medical Director

Role: Study Director

Affiliation: Astellas Pharma Global Development, Inc.

Overall Contact

Name: Astellas Pharma Global Development

Phone: 800-888-7704

Email: astellas.registration@astellas.com

Locations

Facility Status Contact
Alaska Clinical Research Center
Anchorage, Alaska 99508
United States
Recruiting
The Oncology Institute of Hope
Corona, California 92882
United States
Recruiting
University of California
Sacramento, California 95817
United States
Recruiting
Innovative Clinical Research
Whittier, California 90606
United States
Recruiting
University of Colorado
Denver, Colorado 80045
United States
Recruiting
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut 06510
United States
Recruiting
Florida Hospital
Orlando, Florida 32804
United States
Recruiting
Norton Cancer Institute
Louisville, Kentucky 40207
United States
Recruiting
Dana-Farber cancer Institute
Boston, Massachusetts 02215
United States
Recruiting
Allina Health System
Minneapolis, Minnesota 55407
United States
Recruiting
Nebraska Cancer Specialists
Omaha, Nebraska 68130
United States
Recruiting
Montefiore Medical Center
Bronx, New York 10467
United States
Recruiting
Queens Medical Associates
Fresh Meadows, New York 11366-1531
United States
Recruiting
Long Island Jewish Medical Center
Lake Success, New York 11042
United States
Recruiting
White Plains Hospital Center for Cancer Care - Oncology Site
White Plains, New York 10601
United States
Recruiting
Dayton Physicians LLC
Dayton, Ohio 45430
United States
Recruiting
Toledo Clinic Cancer Center
Toledo, Ohio 43623
United States
Recruiting
Providence Portland Med Center
Portland, Oregon 97213
United States
Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
United States
Recruiting
Saint Francis Hospital
Greenville, South Carolina 29607
United States
Recruiting
HOPE Cancer Center of East Texas
Tyler, Texas 75701
United States
Recruiting
Providence St. Mary Regional Center
Lacey, Washington 98503
United States
Recruiting
Medical Oncology Associates, PS
Spokane, Washington 99208
United States
Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Recruiting
Site AU61002
Sydney,
Australia
Recruiting
Site AT43004
Wien,
Austria
Recruiting
Site BE32011
Aalst,
Belgium
Recruiting
Site BE32010
Charleroi,
Belgium
Recruiting
Site BE32001
Gent,
Belgium
Recruiting
Site BE32003
Leuven,
Belgium
Recruiting
Site BE32002
Roeselare,
Belgium
Recruiting
Site CA15012
Edmonton,
Canada
Recruiting
Site CA15007
Montreal,
Canada
Recruiting
Site CA15002
Quebec,
Canada
Recruiting
Site CA15004
Quebec,
Canada
Recruiting
Site CA15001
Sherbrooke,
Canada
Recruiting
Site CA15013
Vancouver,
Canada
Recruiting
Site DK45004
Copenhagen,
Denmark
Recruiting
Site DN45001
Herlev,
Denmark
Recruiting
Site FR33009
Bordeaux,
France
Recruiting
Site FR33001
Brest,
France
Recruiting
Site FR33003
Nice,
France
Recruiting
Site FR33012
Paris,
France
Recruiting
Site FR33005
Pierre-Bénite,
France
Recruiting
Site IT39006
San Giovanni Rotondo,
Italy
Recruiting
Site IT39004
Terni,
Italy
Recruiting
Site JP81015
Chiba,
Japan
Recruiting
Site JP81004
Hiroshima,
Japan
Recruiting
Site JP81014
Kashiwa,
Japan
Recruiting
Site JP81009
Kita-gun,
Japan
Recruiting
Site JP81012
Koto-ku,
Japan
Recruiting
Site JP81001
Kyoto,
Japan
Recruiting
Site JP81018
Morioka,
Japan
Recruiting
Site JP81017
Niigata,
Japan
Recruiting
Site JP81003
Okayama,
Japan
Recruiting
Site JP81007
Sapporo,
Japan
Recruiting
Site JP81005
Sendai,
Japan
Recruiting
Site JP81013
Shinjuku,
Japan
Recruiting
Site JP81006
Toyama,
Japan
Recruiting
Site JP81011
Ube,
Japan
Recruiting
Site KR82006
Daejeon,
Korea, Republic of
Recruiting
Site KR82002
Incheon,
Korea, Republic of
Recruiting
Site KR82001
Seongnam-si,
Korea, Republic of
Recruiting
Site KR82003
Seoul,
Korea, Republic of
Recruiting
Site KR82004
Seoul,
Korea, Republic of
Recruiting
Site KR82008
Seoul,
Korea, Republic of
Recruiting
Site KR82005
Shin,
Korea, Republic of
Recruiting
Site ES34003
Madrid,
Spain
Recruiting
Site ES34005
Seville,
Spain
Recruiting
Site ES34007
Valencia,
Spain
Recruiting
Site TW88604
Taipei,
Taiwan
Recruiting
Site UK44005
London,
United Kingdom
Recruiting