Trial Title:
Sacituzumab Govitecan Before Radical Cystectomy for the Treatment of Non-Urothelial Muscle Invasive Bladder Cancer
NCT ID:
NCT05581589
Condition:
Muscle Invasive Bladder Carcinoma
Stage II Bladder Cancer AJCC v8
Stage IIIA Bladder Cancer AJCC v8
Conditions: Official terms:
Urinary Bladder Neoplasms
Camptothecin
Irinotecan
Immunoconjugates
Sacituzumab govitecan
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Lymphadenectomy
Description:
Undergo pelvic lymph node dissection
Arm group label:
Treatment (sacituzumab govitecan)
Other name:
excision of the lymph node
Other name:
Lymph Node Dissection
Other name:
Lymph Node Excision
Intervention type:
Procedure
Intervention name:
Radical Cystectomy
Description:
Undergo radical cystectomy
Arm group label:
Treatment (sacituzumab govitecan)
Other name:
Complete Cystectomy
Intervention type:
Biological
Intervention name:
Sacituzumab Govitecan
Description:
Given IV
Arm group label:
Treatment (sacituzumab govitecan)
Other name:
hRS7-SN38 Antibody Drug Conjugate
Other name:
IMMU-132
Other name:
RS7-SN38
Other name:
Sacituzumab Govitecan-hziy
Other name:
Trodelvy
Summary:
This phase II trial tests whether sacituzumab govitecan given before radical cystectomy
works in treating patients with non-urothelial bladder cancer. Sacituzumab govitecan
contains a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called
govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific
molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and
delivers govitecan to kill them. Giving sacituzumab govitecan before radical cystectomy
may make the surgery more effective in patients with muscle invasive bladder cancer.
Detailed description:
OUTLINE:
Patients receive sacituzumab govitecan intravenously (IV) over 3 hours on days 1 and 8 of
each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease
progression or unacceptable toxicity. Within 2-6 weeks after last dose, patients undergo
radical cystectomy and pelvic lymph node dissection.
After completion of study treatment, patients are followed up at 1-3 months after radical
cystectomy and then every 3-6 months for 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must be at least 18 years of age on the day of signing informed
consent. Participant (or legally acceptable representative if applicable) provides
written informed consent for trial
- Participants must have either histologically or by clinical consensus (based on
imaging and/or exam under anesthesia) confirmed diagnosis of muscle invasive bladder
cancer (cT2-T4aN0-N1M0 or cT1-4aN1M0 clinical stage per American Joint Commission on
Cancer [AJCC]). Patients with clinical node-positive (N1) stage are eligible
provided the lymph node (LN) is confined to the true pelvis and is within the
planned surgical LN dissection template; cN1 is defined as a lymph node with >= 15
mm short axis or biopsy-positive for carcinoma
- Must have clinical non-metastatic bladder cancer (M0) determined by cross-sectional
Computed tomography (CT) chest, abdomen and pelvis (CAP) or magnetic resonance
imaging (MRI)
- Review of pathology by local expert genitourinary (GU) pathologist is required. Any
component (%) of non-conventional urothelial (variant histology) noted on
transurethral resection of bladder tumour (TURBT) is allowed, for histologic types
not listed below. However, for the variant histologic types listed below, the
following parameters need to be met:
- Squamous cell carcinoma / squamous cell features need to be pure or predominant
(>= 1 variant histologic with total non-conventional urothelial component >
50%).
- Adenocarcinoma / glandular features need to be pure or predominant (>= 1
variant histologic total non-conventional urothelial component > 50%).
- Any % of neuroendocrine / small cell histology is excluded.
- Patients must be considered unfit for cisplatin based on the Galsky et al. criteria
or refuse cisplatin despite adequate counseling in cisplatin-fit patients.
Especially, for tumors containing squamous cell or glandular features, every effort
should be made to discuss the benefit of neoadjuvant cisplatin-based chemotherapy
shown in the S8710 trial
- Participants must be deemed eligible for radical cystectomy (RC) and pelvic lymph
node dissection (PLND) by both urologist and medical oncologist
- TURBT that showed muscularis propria (or lamina propria for cT1N1 tumors) invasion
should be within 12 weeks prior to beginning study therapy. Patients must have
available tumor tissue from either initial or repeat TURBT, prior to starting study
therapy. Archival and/or fresh tumor tissue sample of a tumor lesion (TURBT
specimen) should be provided and must contain muscle invasive component, at least >=
T2 tumor (for cT2 tumors), unless clinical stage is cT1N1M0 (in that case muscle
invasive component is not necessary). Formalin-fixed, paraffin embedded (FFPE)
tissue blocks are preferred to slides. If submitting unstained cut slides, newly cut
slides should be submitted to the testing laboratory, preferably within 14 days from
the date slides are cut if possible. Patient must be willing to provide tumor tissue
for research. Research samples will not be used for unrelated studies
- A male participant must agree to use a contraception during the treatment period and
for at least 180 days after the last dose of study treatment and refrain from
donating sperm during this period
- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 180 days after the last dose of study treatment.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
Patients with ECOG PS 2 may be permitted only after discussion with the trial
primary investigator (PI) (Dr. Grivas). Evaluation of ECOG PS is to be performed
within 7 days prior to the date of enrollment.
- Absolute neutrophil count (ANC) >= 1500/uL (within 10 days prior to the start of
study treatment)
- Platelets >= 100 000/uL (within 10 days prior to the start of study treatment)
- Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (within 10 days prior to the start of study
treatment)
* Criteria must be met without erythropoietin dependency and without packed red
blood cell (pRBC) transfusion within last 2 weeks prior to study drug treatment
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated
creatinine clearance >= 30 ml/min (glomular filtration rate [GFR] can be used in
place of creatinine clearance; 24-hour urine collection can be used for more
accurate estimate as needed) (within 10 days prior to the start of study treatment)
* Creatinine clearance (CrCl) should be calculated per institutional standard
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
bilirubin levels > 1.5 x ULN (within 10 days prior to the start of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])
and Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =<
2.5 x ULN (within 10 days prior to the start of study treatment)
- International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless
participant is receiving anticoagulant therapy (within 10 days prior to the start of
study treatment)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is
receiving anticoagulant therapy (within 10 days prior to the start of study
treatment)
- Patients must agree to undergo curative intent surgery.
Exclusion Criteria:
- Patients with any % of neuroendocrine / small cell histology
- Patients considered to be medically unfit for SG, TURBT or radical cystectomy (per
investigator discretion)
- Prior systemic anti-cancer therapy, including investigational agent/device within 4
weeks or prior radiation therapy within 2 weeks. Intravesical therapies are allowed
without specified treatment interval
- Known locally advanced (unresectable, e.g. cT4b) or metastatic (cN2-3, M1) cancer on
baseline radiographic imaging (CT or MRI) obtained within 28 days prior to
registration
- Active infection requiring systemic antibiotic therapy at the time of trial
initiation. Human immunodeficiency virus (HIV)-positive patients on active therapy
are eligible as long as their viral load is undetectable and CD4 count is within
normal parameters during the time of trial therapy initiation
- Known history of active hepatitis B (defined as hepatitis B surface antigen [HBsAg]
detected or positive hepatitis B virus [HBV] polymerase chain reaction [PCR] test)
or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA)
[qualitative] detected) infection. Note: no testing for hepatitis B and hepatitis C
is required if there is no clinical suspicion of such infection
- History or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results, interfere with the subject's participation for the
full duration of the trial, or is not in the best interest of the subject to
participate, in the opinion of the treating investigator
- Known personality, psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the trial
- Patients may not have concurrent upper urinary tract (i.e., ureter, renal pelvis)
invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper
tract urothelial carcinoma that have been definitively treated with at least one
post-treatment disease assessment (i.e., cytology, biopsy, imaging) that
demonstrates no evidence of residual disease are eligible. Previously treated or
concurrent non-invasive (Ta, Tis) urethra carcinoma is allowed, but history of or
concurrent invasive urethra carcinoma is excluded
- Patients may not have another malignancy that could interfere with the evaluation of
safety or efficacy of of SG. Patients with prior malignancy will be allowed without
PI approval in the following circumstances:
- Not currently active and completed therapy at least 2 years prior to the date
of registration.
- Non-invasive cancer, such as low risk cervical cancer or any carcinoma in situ.
- Localized (early stage) cancer treated with curative intent (without evidence
of recurrence and intent for further therapy), and in which no systemic
chemotherapy was indicated (e.g., low/intermediate risk prostate cancer,
non-melanoma skin cancer, etc.). Low/intermediate risk prostate cancer on
active surveillance or watchful waiting is allowed. Other cancers not meeting
these criteria must be discussed with trial PI (Dr. Grivas)
- Patients may not have undergone major surgery (e.g., intra-thoracic, intra-abdominal
or intra-pelvic), open biopsy or significant traumatic injury =< 3 weeks prior to
starting SG, or who have not recovered from side effects of such procedure or injury
- Have active (based on symptoms, endoscopic or biopsy findings) chronic inflammatory
bowel disease (ulcerative colitis, Crohn's disease) at time of trial therapy
initiation or history of GI perforation within 6 months of enrollment
- Patients may not have clinically significant cardiac diseases, including any of the
following:
- History or presence of serious uncontrolled ventricular arrhythmias.
- Any of the following within 6 months prior to starting study drug: myocardial
infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG),
New York Heart Association (NYHA) Class III or greater congestive heart failure
(CHF) or left ventricular ejection fraction of < 40%, cerebrovascular accident
(CVA), transient ischemic attack (TIA).
- Patients unwilling or unable to comply with the protocol or with known allergy to
SG, its analogues, or excipients in the various formulations
- Patients may not participate in any other therapeutic clinical trials, including
those with other investigational agents not included in this trial before radical
cystectomy
- WOCBP with positive urine pregnancy test within 72 hours prior to enrollment. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required for eligibility. Active lactation is exclusion
- History of allogeneic solid visceral organ transplant, Gilbert's disease, prior
systemic irinotecan or topotecan or other topoisomerase-1 inhibitor, or concomitant
medications that significantly interfere with ABCA1 transporter or UGT1A1 with no
alternate option available
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutch/University of Washington Cancer Consortium
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Patrick Panlasigui
Phone:
206-606-7486
Email:
ppanlas2@fredhutch.org
Investigator:
Last name:
Petros Grivas
Email:
Principal Investigator
Start date:
June 15, 2023
Completion date:
April 30, 2026
Lead sponsor:
Agency:
University of Washington
Agency class:
Other
Collaborator:
Agency:
Gilead Sciences
Agency class:
Industry
Source:
University of Washington
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05581589
