Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer in Cisplatin-unfit and Unwilling for Cystectomy Patients: Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation.
Patients with stable disease or downstaging will continue Zimberelimab up to 1 year. The goal of this trial is to demonstate that Sacituzumab Govitecan + Zimberelimab can avoid cistectomy and can prolong or avoid recurrence to metastatic disease in selected patients with muscle-invasive bladder cancer.
The primary endpoint of this trial is Event Free Survival that is defined as clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event.
详细描述
This is an open-label, multi-center, single-group, phase 2 study. Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation.
Approximately 63 patients will be enrolled and assigned to study intervention. At screening, a tumor specimen from TURBT or biopsy done as early as 90 days prior to enrollment will be submitted for central pathology review. All participants will undergo baseline screening imaging (CT or MRI of the chest, abdomen, pelvis) for clinical staging.
Eligible participants will be allocated to study intervention which consist in SG + Zimberelimab for 3 cycles followed by Zimberelimab for 13 cycles in patients who achieve CR/PR/SD at tumor evaluation.
The planned total duration of treatment is approximately 1 year, 3 cycles of SG and 16 cycles of Zimberelimab.
Treatment will be discontinued if the participant experiences unacceptable AE(s), intercurrent illness that prevents further administration of treatment, the investigator's decision to withdraw the participant, the participant withdraws consent, pregnancy of the participant, noncompliance with study intervention or procedure requirements, or the maximum number of cycles has been received for each treatment component individually.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is at least 18 years old of age, at the time of providing informed consent.
- •The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- •Patients deemed ineligible for Radical Cystectomy (RC) + Retroperitoneal lymphnode dissection (RPNLD) by a urologist and/or oncologist and/or anesthesiology.
- •Cisplatin unfit patients as per Galsky criteria (ECOG Performance Status of 2 and/or creatinine-clearance < 60 ml/min and/or CTCAE Gr ≥ 2 hearing loss and/or CTCAE Gr ≥ 2 neuropathy).
- •Cisplatin-fit patients are admitted if they are unwilling to undergo Radical Cystectomy (RC) and unwilling for cisplatin-based chemotherapy.
- •Patients deemed eligible for surgery will be included if they will be unwilling to undergo RC and will be ineligible and/or unwilling to cisplatin-based chemotherapy.
- •cT2-cT4 bladder cancer patients with predominant urothelial histology or Squamous cell histologic variant with histological confirmed diagnosis of muscle-invasive bladder cancer (MIBC) obtained via a diagnostic or maximal TURBT performed within 90 days before enrollment.
- •cN0-1 bladder cancer patients with predominant urothelial histology or Squamous cell histologic variant
- •Have adequate organ function as defined as follow (Specimens must be collected within 10 days prior to the start of study intervention):
- •Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study treatment initiations (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL).
- •Adequate hepatic function (bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN if known liver metastases, and serum albumin > 3 g/dL).
- •Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation.
- •International normalized ratio (INR)/PT and PTT or aPTT ≤ 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy.
- •Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled
- •HIV infection/disease defined as:
- •Patients on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of screening.
- •Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening.
- •Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1).
- •The combination ART regimen must not contain any medications that may interfere with SN-38 metabolism.
排除标准
- •Positive serum pregnancy test (Appendices 9.4) or women who are breastfeeding.
- •Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
- •Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section.
- •Have had a prior anticancer biologic agent within 4 weeks prior to enrollment or have had prior chemotherapy or targeted small molecule therapy. Patients participating in observational studies are eligible.
- •Have previously received topoisomerase 1 inhibitors.
- •Have an active second malignancy. Note: patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll. Other exception are localized prostate cancer with a Gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.
- •Patients with neuroendocrine histology will be excluded.
- •Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment.
- •Have active serious infection requiring antibiotics.
- •Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
- •Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded.
- •Patients who test positive for hepatitis B surface antigen (HBsAg). Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease.
- •Patients who test positive for HCV antibody. Patients who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Patients with a known history of HCV or a positive HCV antibody test will not require a HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.
- •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.
- •Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the patient's participation in the study.
- •Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.
研究组 & 干预措施
Sacituzumab Govitecan + Zimberelimab
patients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice.
干预措施: Sacituzumab Govitecan + Zimberelimab (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: 24 months
clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event. Patients last known to be EFS event-free are censored at the date of last event-free cystoscopy and/or CT scan. Those patients without disease assessment who are still alive will be censored at date of inclusion in the trial
次要结局
- clinical or pathological downstaging(24 months)
- Number of Participants treated with Pembrolizumab + Enfortumab Vedotin who experience AEs/SAEs(24 months)
- predictive role of miRNA in patients who achieve clinical or pathological downstaging after SG + Zimberelimab treatment(24 months)
- predictive role of ctDNA in patients who achieve clinical or pathological downstaging after SG + Zimberelimab treatment(24 months)
- role of 18FDG-PET in the prediction of response or relapse for N positive patients(24 months)
- the role of multiparametric MRI (mpMRI) in the assessment of clinical response(24 months)