2025-524232-20-00招募中2 期
REGENOVAR: A Phase I/II Study of Ubamatamab Plus Carboplatin, Paclitaxel, and Bevacizumab as Salvage Therapy in Ovarian Cancer with Poor Response to First-Line Chemotherapy.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 11
- 主要终点
- Treatment emergent adverse events according to NCI CTCAE version 6.0.
研究概览
简要总结
Safety run-in phase I part and Efficacy phase II part.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed high-grade epithelial (serous, endometrioid, or carcinosarcoma with a ≥30% epithelial tumor component) ovarian, primary peritoneal, or fallopian-tube carcinoma.
- •Adequate renal and liver functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN in context of liver metastases; Total bilirubin ≤1.5 × ULN (patients with Gilbert’s are eligible if total bilirubin ≤3 × ULN); Albumin ≥3 g/dL; Creatinine clearance ≥40 mL/min/1.73 m2 (measured or estimated, ideally with CKD-EPI formula on https://www.kidney.org/professionals/kdoqi/gfr_calculator).
- •Adequate heart function: LVEF ≥ 50%, measured by echocardiogram, and troponin levels above the upper limit of normal (ULN). The case of troponin level comprised between 1.0 and 2 ULN, inclusion may be discussed after cardiological assessment.
- •Life expectancy of at least 3 months.
- •Patients who gave their written informed consent to participate to the study.
- •Patients affiliated to a social insurance regime.
- •Patients who are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
- •Adult patient aged ≥ 18 years old
- •Advanced stage III or IV
- •Treated with 3 or 4 standard neo-adjuvant cycles of carboplatin-paclitaxel regimen, in first line, given every 3 weeks, and characterized by 2 unfavorable features (both are required): • A poorly chemosensitive disease defined by an unfavorable standardized KELIM score < 1.0 calculated on CA-125 KELIM™ calculator for patients treated with neo-adjuvant chemotherapy • A disease considered not amenable to complete interval cytoreductive surgery with no post-operative macroscopic residual lesion (either because the interval cytoreductive surgery attempt was incomplete CC2-CC3, or because the surgeon considers a complete interval cytoreductive surgery is not achievable based on imaging and/or laparoscopic explorations)
- •Disease measurable and assessable by imaging based on RECIST 1.1 criteria (thorax-abdomen-pelvis CT-scanner; FDG-PET-CT-scanner; and/or MRI).
- •Availability of a tumor tissue for translational research (archival tissue, or alternatively from fresh biopsy, and/or surgery).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •BRCA and HRD status known, or planned during the trial (before maintenance treatment)
- •Adequate bone marrow function: Red blood cells: baseline Hemoglobin ≥7 g/dL; White blood cells: Absolute neutrophil count (ANC) ≥1500 cells/mm3; Platelets: Platelet count ≥100,000/mm3.
排除标准
- •Low-grade endometrioid, clear cell, mucinous, or sarcomatous histology, or mixed tumors containing any of these histologies, or low-grade serous or borderline ovarian tumor.
- •Persistent toxicities (≥CTCAE grade 3), caused by previous cancer therapy.
- •Treatment with other investigational agents.
- •Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication, such as malabsorption.
- •Clinically significant (i.e., active) and severe cardiovascular disease according to investigator opinion such as: a. myocardial infarction (< 6 months prior to enrollment); b. any history of myocarditis; c. significant arrhythmia including paroxysmal atrial fibrillation requiring intervention at any time or implantation of a pacemaker or defibrillator; d. signs or symptoms of active angina; arrhythmia or heart failure; e. QTc (Friedericia) interval >470 msec (in cases of asymptomatic prolonged QTc interval (>470 msec), the ECG can be repeated up to 2 times. If subsequent QTc interval is <470 msec, the patient may be enrolled but only after review and approval by a cardiologist); Evidence of Second-Degree AV block type II (Mobitz type II) or AV block type III (complete heart block); f. Baseline serum troponin above institutional upper limit of normal. In cases of minimally elevated troponin 1-2 X ULN in absence of clinical symptoms, after clearance by a cardiologist, the patient may be enrolled.
- •Untreated pulmonary embolism (PE) or deep vein thrombosis (DVT), but patients on stable with anticoagulant therapy are allowed.
- •Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immunological adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, hypothyroidism that required only hormone replacement, type 1 diabetes or psoriasis that does not require systemic immunosuppressive treatment.
- •Uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency or known latent tuberculosis infection. Participants will be tested for HCV and HBV at screening per Section 5.2: Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted; Patients with hepatitis B surface antigen positive (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted; Participants with HBsAg negative but total HBV core antibody positive (HBc Ab+) are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, antiviral therapy for HBV must be initiated prior to study entry. If serum HBV DNA PCR is below the limit of detection periodic monitoring of HBsAg must be performed; Patients who are Hepatitis C virus antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
- •Other active infections requiring hospitalization or IV anti-infectives within 2 weeks before starting study treatment.
- •Receipt of a live vaccine within 30 days of planned start of study medication.
- •Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial.
- •Patients with primary platinum-refractory disease, defined as disease that has radiologically progressed during neo-adjuvant chemotherapy.
- •Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include: a. stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; b. intrauterine device (IUD); intrauterine hormone-releasing system (IUS); c. bilateral tubal occlusion/ligation; d. vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure) and/or; e. sexual abstinence** **. * WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to Clinical Trial Facilitation Group (CTFG) guidance. ** Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. ***Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
- •Known psychiatric disorder that would interfere with trial compliance.
- •Patient deprived of liberty, under guardianship, or under curatorship.
- •Contraindication to carboplatin, paclitaxel or bevacizumab.
- •Previous treatment with bevacizumab during initial standard neo-adjuvant chemotherapy.
- •Prior treatment with anti-PD-1 therapies or T-cell therapies, or any other experimental anti-cancer systemic therapy.
- •Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years.
- •All trial participants with brain metastases, except those meeting the following criteria (all criteria are required): a. Brain metastases that have been treated locally, and are clinically asymptomatic for at least 4 weeks prior to enrolment; b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable); c. Trial participants with brain metastases must be either off steroids except a stable or decreasing dose of <10mg daily prednisone (or equivalent).
- •Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
- •Patients receiving any systemic chemotherapy, radiotherapy (except for symptomatic/palliative reasons), within 3 weeks before the first dose of ubamatamab.
研究组 & 干预措施
FILGRASTIM
Auxiliary
干预措施: FILGRASTIM (Drug)
CARBOPLATIN
Auxiliary
干预措施: CARBOPLATIN (Drug)
PACLITAXEL
Auxiliary
干预措施: PACLITAXEL (Drug)
Ubamatamab, Ubamatamab
Test
干预措施: Ubamatamab (Drug)
BEVACIZUMAB
Auxiliary
干预措施: BEVACIZUMAB (Drug)
结局指标
主要结局
Treatment emergent adverse events according to NCI CTCAE version 6.0.
Treatment emergent adverse events according to NCI CTCAE version 6.0.
Dose-limiting toxicities (DLT) occurring during the DLT period (first 4 weeks of treatment).
Dose-limiting toxicities (DLT) occurring during the DLT period (first 4 weeks of treatment).
The recommended dose for phase II trial (RP2D) of ubamatamab in combination with carboplatin-paclitaxel-bevacizumab.
The recommended dose for phase II trial (RP2D) of ubamatamab in combination with carboplatin-paclitaxel-bevacizumab.
Objective response rate (ORR): Percentage of patients experiencing complete (CR) or partial response (PR) as the best overall radiological response after 3 cycles of ubamatamab in combination with carboplatin-paclitaxel-bevacizumab based on RECIST 1.1 criteria.
Objective response rate (ORR): Percentage of patients experiencing complete (CR) or partial response (PR) as the best overall radiological response after 3 cycles of ubamatamab in combination with carboplatin-paclitaxel-bevacizumab based on RECIST 1.1 criteria.
次要结局
- Treatment emergent Adverse events according to NCI CTCAE version 6.0 during the whole treatment period.
- Objective response rate (ORR): Percentage of patients experiencing complete (CR) or partial response (PR) as the best overall radiological response during the whole study treatment period based on RECIST 1.1 criteria.
- Duration of response in patients experiencing an objective response: Time from first objective response to first objective documented disease progression (based on RECIST v1.1 criteria), or to death (regardless of the cause in the absence of disease progression).
- Disease control rate (DCR): Percentage of patients experiencing complete (CR) or partial response (PR) or stable disease (SD) as the best overall radiological response during the whole treatment period based on RECIST 1.1 criteria.
- Percentage of patients operated with late cytoreductive surgery (after 3 cycles of the study regimen), and among them the percentage of patients operated with complete surgery without any macroscopic residual lesion.
- Progression-free survival (PFS): Time from treatment start until the date of event defined as the first objective documented disease progression (based on RECIST v1.1 criteria) or death (regardless of the cause in the absence of progression). Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment.
- Overall survival (OS): Time from the date from treatment start until death regardless of the cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
- Progression-free survival during subsequent line of treatment (PFS-ST): Time from the start of the subsequent line of treatment until the date of event defined as the first objective documented progression (based on RECIST v1.1), or death (regardless of the cause in the absence of progression).
研究者
Benoit YOU
Scientific
Asso De Recherche Cancers Gynecologiques
研究点 (11)
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