An open label, single-arm, phase 2 study of neoadjuvant sacituzumab govitecan, before radical cystectomy, for patients with muscle-invasive bladder cancer who cannot receive or refuse cisplatin-based chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Mar 2022 → 24 Sep 2025

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515301-26-00

EudraCT number

2020-004844-27

ClinicalTrials.gov

NCT05226117

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess whether sacituzumab govitecan results in pathological complete response (herein referred to as either “pT0” or “pCR”) in patients with MIBC who cannot receive or refuse cisplatin-based chemotherapy

Secondary objectives 3

1. To evaluate radiological response on those patients with measurable disease
2. To evaluate the surgical and medical safety of neoadjuvant therapy
3. To assess survival outcomes (event-free survival and overall survival)

Conditions and MedDRA coding

Muscle-invasive bladder cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Female or male subjects, >18 years of age, able to understand and give written informed consent
2. Histopathologically confirmed urothelial carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
3. Fit and planned for RC (according to local guidelines).
4. ECOG performance status score of 0 or 1.
5. Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (Hemoglobin ≥ 9 g/dL, ANC ≥ 1,500/ mm3, and Platelets ≥ 100,000/ μL).
6. Adequate hepatic function (Bilirubin ≤ 1.5 IULN, AST and ALT ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin >3 g/dl).
7. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation.
8. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication, and must not be lactating. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
9. Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years.
10. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study therapy.
11. Clinical stage defining clinical T2-T4N0M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1).
12. The patient accepts to undergo radical cystectomy.
13. Ineligibility to receive cisplatin-based neoadjuvant chemotherapy based on Galsky’s criteria OR refusal to receive neoadjuvant cisplatin-based chemotherapy.

Exclusion criteria 15

1. Have received prior systemic anti-cancer therapy including investigational agents and immunotherapy.
2. Have received prior radiotherapy on the bladder tumor.
3. Refusal to undergo RC.
4. Are currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
5. Have a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or T2a with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) < 10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.
6. Women who are pregnant or lactating
7. Have severe hypersensitivity (≥Grade 3) to sacituzumab govitecan and/or any of its excipients.
8. Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
9. Have nephrostomy, central venous catheters, any other types of catheters that could make the patient at higher risk of developing severe infectious complications during treatment with sacituzumab govitecan.
10. Have ≥3 risk factors for the development of febrile neutropenia according to the ASCO guidelines (Smith et al, J Clin Oncol. 2015;33:3199-3212). These risk factors are the following: Age >65 years, advanced disease, Previous chemotherapy or radiation therapy, Preexisting neutropenia or bone marrow involvement with tumor, infection, Open wounds or recent surgery, Poor performance status or poor nutritional status, Poor renal function, Liver dysfunction, most notably elevated bilirubin, Cardiovascular disease, Multiple comorbid conditions, HIV infection.
11. Have a history of inflammatory bowel disease, ulcerative colitis, or any other pre-existing inflammatory or autoimmune disease that could make the patient at higher risk of developing severe diarrhea or related complications.
12. Have active cardiac disease, defined as: • Myocardial infarction or unstable angina pectoris within 6 months of C1D1 • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation • NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%
13. Have known history of HIV-1/2.
14. Have active HBV or HCV. In subjects with a history of HBV or HCV, subjects with detectable viral loads will be excluded.
15. Have 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of complete pathological responses, defined as the absence of viable tumor cells on the histological examination of the cystectomy. Evidence of carcinoma in situ or non-muscle infiltrating disease does not define a complete pathological response.

Secondary endpoints 1

1. Evaluation of safety and tolerability of the treatment: Number of patients who experienced adverse events. Type, frequency, severity and relationship to the treatment of the adverse events, evaluated according the Common Toxicity Criteria for adverse events (CTCAE) v 5.0. Progression free survival Overall survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Genitourinary Medical Oncology

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Genitourinary Medical Oncology

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications