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.
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 Outcome 1 - Measure: Overall Survival (OS)
Primary Outcome 1 - Time Frame: Up to 36 months
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
Name: Senior Medical Director
Role: Study Director
Affiliation: Astellas Pharma Global Development, Inc.
Name: Astellas Pharma Global Development
Phone: 800-888-7704
Email: astellas.registration@astellas.com
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 | |
Sylvester Comprehensive Cancer Center Miami, Florida 33136 United States |
Recruiting | |
Florida Hospital Orlando, Florida 32804 United States |
Recruiting | |
Norton Cancer Institute Louisville, Kentucky 40207 United States |
Recruiting | |
Ochsner Clinic Foundation New Orleans, Louisiana 70121 United States |
Recruiting | |
Dana-Farber cancer Institute Boston, Massachusetts 02215 United States |
Recruiting | |
UMass Memorial Medical Center Worcester, Massachusetts 01605 United States |
Recruiting | |
Fairview Ridges Specialty Center Burnsville, Minnesota 55337 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 | |
Roswell Park Cancer Institute Buffalo, New York 14263 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 BE32005 Hasselt, Belgium |
Recruiting | |
Site BE32003 Leuven, Belgium |
Recruiting | |
Site BE32002 Roeselare, Belgium |
Recruiting | |
Site CA15015 Calgary, Canada |
Recruiting | |
Site CA15012 Edmonton, Canada |
Recruiting | |
Site CA15003 Hamilton, Canada |
Recruiting | |
Site CA15007 Montreal, Canada |
Recruiting | |
Site CA15002 Quebec, Canada |
Recruiting | |
Site CA15004 Quebec, Canada |
Recruiting | |
Site CA15008 Saskatoon, Canada |
Recruiting | |
Site CA15001 Sherbrooke, Canada |
Recruiting | |
Site CA15013 Vancouver, Canada |
Recruiting | |
Site DK45004 Copenhagen, Denmark |
Recruiting | |
Site DN45001 Herlev, Denmark |
Recruiting | |
Site FR33021 Besancon, France |
Recruiting | |
Site FR33009 Bordeaux, France |
Recruiting | |
Site FR33018 Bordeaux, France |
Recruiting | |
Site FR33001 Brest, France |
Recruiting | |
Site FR33016 Caen, France |
Recruiting | |
Site FR33003 Nice, France |
Recruiting | |
Site FR33012 Paris, France |
Recruiting | |
Site FR33005 Pierre-Bénite, France |
Recruiting | |
Site FR33004 Saint-Mande, France |
Recruiting | |
Site IT39010 Milan, Italy |
Recruiting | |
Site IT39006 San Giovanni Rotondo, Italy |
Recruiting | |
Site IT39004 Terni, Italy |
Recruiting | |
Site JP81010 Hirosaki, Aomori Japan |
Recruiting | |
Site JP81014 Kashiwa, Chiba Japan |
Recruiting | |
Site JP81007 Sapporo, Hokkaido Japan |
Recruiting | |
Site JP81020 Tsukuba, Ibaraki Japan |
Recruiting | |
Site JP81018 Morioka, Iwate Japan |
Recruiting | |
Site JP81009 Kita-gun, Kagawa Japan |
Recruiting | |
Site JP81002 Yokohama, Kanagawa Japan |
Recruiting | |
Site JP81005 Sendai, Miyagi Japan |
Recruiting | |
Site JP81008 Bunkyo-ku, Tokyo Japan |
Recruiting | |
Site JP81012 Koto-ku, Tokyo Japan |
Recruiting | |
Site JP81013 Shinjuku-ku, Tokyo Japan |
Recruiting | |
Site JP81011 Ube, Yamaguchi Japan |
Recruiting | |
Site JP81015 Chiba, Japan |
Recruiting | |
Site JP81004 Hiroshima, Japan |
Recruiting | |
Site JP81001 Kyoto, Japan |
Recruiting | |
Site JP81017 Niigata, Japan |
Recruiting | |
Site JP81003 Okayama, Japan |
Recruiting | |
Site JP81006 Toyama, Japan |
Recruiting | |
Site KR82006 Daejeon, Korea, Republic of |
Recruiting | |
Site KR82007 Goyang-Si, 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 KR82009 Seoul, Korea, Republic of |
Recruiting | |
Site KR82005 Shin, Korea, Republic of |
Recruiting | |
Site NL31003 Amsterdam, Netherlands |
Recruiting | |
Site PT35102 Lisbon, Portugal |
Recruiting | |
Site ES34003 Madrid, Spain |
Recruiting | |
Site ES34005 Seville, Spain |
Recruiting | |
Site ES34007 Valencia, Spain |
Recruiting | |
Site TW88605 Kaohsiung, Taiwan |
Recruiting | |
Site TW88601 Tainan, Taiwan |
Recruiting | |
Site TW88604 Taipei, Taiwan |
Recruiting | |
Site UK44005 London, United Kingdom |
Recruiting |