Trial Title:
PeRioperative Immunotherapy Combined With Sacituzumab Govitecan in Muscle Invasive blAdder Cancer
NCT ID:
NCT06133517
Condition:
Urothelial Bladder Carcinoma
Conditions: Official terms:
Urinary Bladder Neoplasms
Sacituzumab govitecan
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sacituzumab govitecan
Description:
Sacituzumab govitecan is administered at 10 mg/kg as an intravenous (IV) infusion on Days
1 and 8 of a 21-day cycle.
Arm group label:
Single Arm
Other name:
Trodelvy
Intervention type:
Drug
Intervention name:
Zimberelimab
Description:
ZIM is administered at 360 mg every 3 weeks as an intravenous (IV) infusion on Day 1 of a
21-day cycle.
Arm group label:
Single Arm
Intervention type:
Drug
Intervention name:
Domvanalimab
Description:
DOM is administered at 1200 mg every 3 weeks as an intravenous (IV) infusion on Day 1 of
a 21-day cycle.
Arm group label:
Single Arm
Summary:
The main objective of this trial is to evaluate the efficacy of the combo Sacituzumab
govitecan (SG) + Zimberelimab (AB 122) (ZIM) + Domvanalimab (AB 154) (DOM), measured as
pathologic complete response (pCR) rates, in the perioperative setting in patients with
Muscle Invasive Bladder Cancer (MIBC) who are either unfit for platinum-based
chemotherapy or unwilling to receive that therapy.
Detailed description:
This is an open label, multicenter, single arm, phase II clinical trial, which aims to
evaluate the effects of perioperative treatment with sacituzumab govitecan, zimberelimab
and domvanalimab in patients with confirmed histological diagnosis of urothelial bladder
carcinoma pT2-T4a cN0-1 cM0 non-eligible or who refuse to receive cisplatin-based
neoadjuvant chemotherapy.
Patients who are eligible to participate in the study will receive 3 cycles of
sacituzumab govitecan, zimberelimab and domvanalimab every 3 weeks prior to cystectomy,
unless there are signs of unacceptable toxicity, progressive disease or the patient
requests withdrawal from the study. Patients who do not achieve a pCR or that achieving a
pCR still have positive ctDNA will also complete an adjuvant phase of the study
consisting of 12 additional cycles of zimberelimab and domvanalimab.
To progressively test the safety of the proposed combination, this study has been
developed in two stages with the aim of preserving patient's safety as a priority. This
study includes a preliminary assessment about the safety of the combinations. Thus, there
will be a safety run-in period in which 8 patients will receive the SG+ZIM combination to
confirm the tolerability of this doublet in patients with MIBC.
Once the safety of this doublet has been confirmed by an external safety committee then
the study will proceed to an additional safety-run in cohort with the triplet.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Willing and able to provide written informed consent.
2. Ability to comply with the study procedures and requirements and restrictions in
this protocol.
3. Age ≥ 18 years.
4. Muscle invasive urothelial carcinoma stage cT2-T4cN0-1cM0. Patients with mixed
histologies are required to have a dominant (i.e. 50% at least) urothelial carcinoma
pattern.
5. Fit and planned for cystectomy (according to local guidelines).
6. Refusal of neoadjuvant cisplatin-based chemotherapy or patients in whom neoadjuvant
cisplatin-based therapy is not appropriate. (This will be determined by the
investigator and not solely based in Galsky Criteria).
7. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks
preferred) or at least 15 unstained slides, with an associated pathology report, for
testing at the study sponsor site. Patients with fewer than 15 unstained slides
available at baseline (but no fewer than 10) may be eligible following discussion
with the PI of the study.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
9. Adequate hematologic and end-organ function tests defined by the following:
1. White Blood Cell (WBC) ≥ 2.0x109/L,
2. Neutrophils ≥1.5x109/L,
3. Platelets ≥100 x109/L,
4. Hemoglobin ≥ 10 g/dL,
5. Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation
6. Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal(ULN),
7. Alanine aminotransferase (ALT) ≤2.5 x ULN,
8. Bilirubin ≤1.5 X ULN.
10. Adequate coagulation (Prothrombin Time [PT]) or International Normalized Ratio [INR]
and Activated Partial Thromboplastin Time [aPTT]) ≤ 1.5 x ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants.
11. Negative pregnancy test within 3 days of Day 1 Cycle 1 for female patients of
childbearing potential.
12. Male patients and female patients of childbearing potential who engage in
heterosexual intercourse must agree to use protocol-specified method(s) of
contraception.
Exclusion Criteria:
1. Concurrent enrollment in another interventional clinical trial, unless in a
follow-up period or it is an observational study.
2. Having received previous anticancer therapy including:
1. Any investigational anticancer therapy received within 28 days or 5 half-lives
(whichever is longer) of first dose of study treatment.
2. Any previous intravenous chemotherapy specific for bladder cancer.
3. Previous systemic treatment with topoisomerase 1 inhibitors.
4. Prior Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or Programmed death-1(PD-1)/
programmed death-ligand 1(PD-L)1-targeting immunotherapy.
5. Previous treatment with high dose chemotherapy and bone marrow transplant
6. Previous radiotherapy specific for bladder cancer
3. Underlying medical conditions that might make the administration of study drugs
hazardous or that might obscure the interpretation of adverse events including:
- 3.1 Known or suspected autoimmune disease. Patients with a history of
inflammatory bowel disease (including Crohn's disease and ulcerative colitis)
and autoimmune disorders such as rheumatoid arthritis, systemic progressive
sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis
(e.g., Wegener's granulomatosis) are excluded from this study; Patients with
other autoimmune disorders such as a history of Hashimoto's thyroiditis [only
requiring hormone replacement], type I diabetes, psoriasis [not requiring
systemic treatment], or conditions not expected to recur in the absence of an
external trigger are allowed to participate.
- 3.2 History of primary immunodeficiency.
- 3.3 A positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic
acid (RNA), active tuberculosis, or other active infection requiring therapy at
the time of inclusion.
HIV positive patients are allowed as far as they have the disease controlled
according to their treating physicians based on lymphocyte counts and viral load.
- 3.4 Medical conditions requiring the use of immunosuppressive medications, with
the exceptions of intranasal and inhaled corticosteroids or systemic
corticosteroids at physiological doses not to exceed 10 mg/day of prednisone,
or an equivalent corticosteroid. Steroids as premedication for hypersensitivity
reactions (eg, CT scan premedication) will be allowed.
4. Patient receiving treatment with inhibitors or inducers of UGT1A1 at the time of
enrollment.
5. Patient receiving treatment with high dose systemic corticosteroids (>10 mg of
prednisone or its equivalent) within 2 weeks of C1D1.
6. Patients who have received a vaccination within 30 days prior to inclusion (examples
include, but are not limited to, intranasal influenza vaccines, typhoid [oral]
vaccines, and Bacillus Calmette-Guerin [BCG]). Patients are allowed to receive the
COVID-19 vaccine to reduce the risk and complications of COVID-19 infection. The
study visits should continue as planned if vaccination occurs while the patient is
on the study.
7. Malignancy, other than urothelial cancer, in the previous 2 years. Patients with
low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and Prostatic
specific antigen (PSA) ≤ 10 ng/mL) appropriately treated or that are treatment-naive
and undergoing active surveillance are eligible. Also, noninvasive malignancies such
as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal
carcinoma in situ of the breast, that have undergone potentially curative therapy
are not excluded.
8. Major surgical procedure within 4 weeks prior to enrollment or anticipation of need
for a major surgical procedure during the course of the study other than for
diagnosis or treatment of its urothelial cancer.
9. Severe infection within 4 weeks prior to enrollment in the study including but not
limited to hospitalization for complications of infection, bacteremia, or severe
pneumonia.
10. Met any of the following criteria for cardiac disease:
1. Myocardial infarction or unstable angina pectoris within 6 months of
enrollment.
2. History of serious ventricular arrhythmia (ie, ventricular tachycardia or
ventricular fibrillation), high-grade atrioventricular block, or other cardiac
arrhythmias requiring antiarrhythmic medications (except for atrial
fibrillation that is well controlled with antiarrhythmic medication).
3. History of QT interval prolongation.
11. Patient currently on dialysis.
12. Gastrointestinal perforation within 6 months of enrollment.
13. Patients who have organ allografts.
14. Other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation or prevent completion of
study procedures and follow-up examinations.
15. Known allergy or hypersensitivity to study drugs formulations.
16. Patients who have invasive catheters that under the investigator criteria might put
the patient at risk of developing severe complications due to neutropenia
development.
17. Females who are pregnant, lactating, or intend to become pregnant during their
participation in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Clínico Universitario de Santiago
Address:
City:
Santiago De Compostela
Country:
Spain
Contact:
Last name:
Urbano Anido
Investigator:
Last name:
Urbano Anido, MD
Email:
Principal Investigator
Facility:
Name:
ICO Badalona
Address:
City:
Badalona
Country:
Spain
Contact:
Last name:
Albert Font
Investigator:
Last name:
Albert Font, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Duran i Reynals (ICO L´Hospitalet)
Address:
City:
L'Hospitalet De Llobregat
Country:
Spain
Contact:
Last name:
Xavier García del Muro
Investigator:
Last name:
Xavier García del Muro, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Marqués de Valdecilla
Address:
City:
Santander
Country:
Spain
Contact:
Last name:
Ignacio Durán
Investigator:
Last name:
Ignacio Duran, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Donostia
Address:
City:
Donostia
Country:
Spain
Contact:
Last name:
Naiara Sagastibeltza
Investigator:
Last name:
Naiara Sagastibeltza, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario de Navarra
Address:
City:
Pamplona
Country:
Spain
Contact:
Last name:
Nuria Lainez
Investigator:
Last name:
Nuria Lainez, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Clínico San Carlos
Address:
City:
Madrid
Country:
Spain
Contact:
Last name:
Javier Puente
Investigator:
Last name:
Javier Puente, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Virgen de la Salud
Address:
City:
Toledo
Country:
Spain
Contact:
Last name:
Iciar García
Investigator:
Last name:
Iciar Garcia, MD
Email:
Principal Investigator
Facility:
Name:
Fundación Instituto Valenciano de Oncología
Address:
City:
Valencia
Country:
Spain
Contact:
Last name:
Miguel Ángel Climent
Investigator:
Last name:
Miguel Angel Climent, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Clinico Universitario de Valladolid
Address:
City:
Valladolid
Country:
Spain
Contact:
Last name:
Ricardo Sánchez-Escribano
Investigator:
Last name:
Ricardo Sánchez-Escribano, MD
Email:
Principal Investigator
Start date:
October 2024
Completion date:
December 2030
Lead sponsor:
Agency:
Fundación para el Progreso de la Oncología en Cantabria
Agency class:
Other
Collaborator:
Agency:
Apices Soluciones S.L.
Agency class:
Industry
Source:
Fundación para el Progreso de la Oncología en Cantabria
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06133517
