CTRI/2021/12/038483进行中（未招募）3 期
A Prospective, Randomized, Controlled, Open-label, Multicenter Trial to Evaluate Efficacy, Safety and Patient-reported Outcomes of Peptide Receptor Radionuclide Therapy with Lutetium (177Lu) Edotreotide versus Standard of Care in Patients with Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor positive, Neuroendocrine Tumors of GastroEnteric or Pancreatic Origin.
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 202
- 试验地点
- 3
- 主要终点
- Progression free survival (PFS), defined as the time from randomization until adequately documented Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 disease progression (based on blinded, central assessment) or death whichever occurs first
研究概览
简要总结
The purpose of the study is to evaluate the efficacy, safety & patient-reported outcomes of peptide receptor radionuclide therapy (PRRT) with 177Lu-Edotreotide as 1st or 2nd line of treatment compared to the best standard of care in patients with well-differentiated aggressive grade 2 and grade 3, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 90.00 Year(s)（—）
- 性别
- All
入选标准
- •Provided written informed consent.
- •Histologically confirmed diagnosis of unresectable, well-differentiated GEP-NETs, with a Ki-67 index between 15 and 55, inclusive.
- •This should be at least confirmed by a local pathological report of a biopsy specimen of the primary tumor or metastasis, or,if unavailable, willingness to undergo current biopsy for local analysis before randomization.
- •In the investigator’s opinion, eligible to receive treatment with at least one of the following: CAPTEM, everolimus or FOLFOX according to individual risk‑benefit assessment, institutional protocols, the local Prescribing Information, local regulations or the local guidelines.
- •At least 1 measurable site of disease per RECIST v1.1 using contrast CT/MRI.
- •Patients who are allergic to IV contrast may be imaged without.
- •SSTR+ disease, as evidenced by 68Ga-based or 64Cu-based (if approved according to local regulations) SSTR PET SRI (68Ga‑DOTATOC, 68Ga-DOTATATE or 64Cu-DOTATATE) within 4 months prior to randomization and as close as possible to the fluorodeoxyglucose (FDG) PET.
- •a) The majority of the CT/MRI lesions have to be SSTR+.
- •b) The SSTR PET SRI should be repeated at randomization if the scan is not within 28 days of the randomization date.
- •All patients need to undergo a FDG PET scan within 4 months prior to randomization and as close as possible to the PET SRI.
- •a) The majority of FDG PET-positive lesions have to be SSTR+.
- •Patients may be treatment naïve (first-line) or have a maximum of one prior line of therapy, including SSAs, (second-line).
- •a) Patients on any prior antineoplastic therapy (including SSAs) must have radiological disease progression (according to RECIST v1.1) within the 4 months prior to randomization, based on the investigator’s assessment.
- •b) Patients who progress on SSAs may enter the trial continuing on the same dose if required for symptom control.
- •Karnofsky performance status (KPS) scale ≥ 60 (see Appendix 3).
排除标准
- •Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA, any of the comparators the comparator, or any excipient or derivative (e.g. rapamycin). 2) Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective AAS given concurrently with the lutetium (177Lu) edotreotide infusion. 3) Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow. 4) Prior selective internal radiation therapy (SIRT). 5) Prior peptide receptor radionuclide therapy (PRRT). 6) Received chemotherapy, mTOR inhibitors, vascular endothelial growth factor (VEGF) pathway inhibitors, immunotherapy, interferon, chemo-embolization, bland embolization, cyclosporine A, locoregional treatment (e.g. cytoreduction surgery, radiofrequency ablation [RFA], liver directed intra-arterial intervention) or SSAs within 4 weeks prior to randomization into the trial. Patients may be treated with SSAs for symptom control, but they must have remained on the same dose of the SSA as at the time of demonstrated disease progression. 7) Any major surgery within 4 weeks prior to randomization in the trial. 8) Therapy with an investigational compound and/or medical device within 30 days or 7 half-life periods (whichever is longer) prior to randomization. 9) Patients who have received a live attenuated vaccine up to 4 weeks prior to randomization. 10) Patients with brain metastases. 11) Other known malignancies (except non-invasive skin cancer and carcinoma of the cervix in situ), unless definitively treated and proven no evidence of recurrence for 5 years. 12) Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune, metabolic or dementia), that may interfere with the objectives of the trial or with the safety or compliance of the patient, as judged by the investigator. 13) Renal, hepatic, cardiovascular, or hematological organ dysfunction, potentially interfering with the safety of the trial treatments, as follows: a) Renal.
- •GFR < 50 mL/min/1.73 m2 (calculated by the Chronic Kidney DiseaseEpidemiology Form [CKD-EPI] formula [local laboratory]), Creatinine clearance < 50 mL/min calculated by the Cockcroft Gault method, Renal tract obstruction. b) Hepatic, Total bilirubin > 3 × upper limit of normal (ULN), Albumin < 30 g/L, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 × ULN, Known ascites c) Cardiovascular, Heart failure (New York Heart Association [NYHA] classification III and IV), Uncontrolled hypertension, Hematopoietic, Platelets ≤ 75 × 109/L, Absolute neutrophil count (ANC) < 1.5 × 109 cells/L, Hemoglobin (Hb) concentration < 5.0 mmol/L (< 8.0 g/dL) e) Any other ongoing hematological or renal Grade 2 toxicity or other Grade 3 toxicity from previous standard or investigational therapies (NCI-Common Terminology Criteria for Adverse Events [CTCAE] version 5.0). 14) Current spontaneous urinary incontinence. 15) Pregnancy and breast-feeding: Female patients of childbearing potential or male patients with female partners of childbearing potential, unless willing to practice full and true sexual abstinence or who are surgically/permanently sterile (hysterectomy, or vasectomy), or female patients whose male partners have medically successful vasectomy (provided the partner is the sole sexual partner of the female patient of childbearing potential), or who are not willing to practice highly effective contraception in combination with a barrier method of contraception (e.g. condom). Contraception methods that are considered highly effective are: i. Oral or non-oral (injected or implanted) non-estrogen progesterone-based hormonal method; oral, intravaginal, or transdermal combined estrogen and progesterone-based hormonal methods; and/or ii. Intrauterine device (IUD), and/or intrauterine hormone-releasing system (IUS). iii. Bilateral fallopian tubal ligation. Note: Sexual abstinence or the contraception methods described above must be followed throughout the entire trial period and for the following durations after last trial drug administration: 6 months for CAPTEM; 8 weeks for everolimus; 6 months for FOLFOX; 66 days for PRRT (10 half-lives of 177Lu (Brown, 2020; Ferreira et al., 2017). b) Women who are breast-feeding. 16) Patients not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalized, incarcerated etc.).
结局指标
主要结局
Progression free survival (PFS), defined as the time from randomization until adequately documented Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 disease progression (based on blinded, central assessment) or death whichever occurs first
时间窗: All patients will undergo efficacy assessment by RECIST v1.1 every 12± 2 weeks through CT/MRI from the randomization date (first scan will be performed after Cycle 2 for the IMP arm) until documented disease progression.
次要结局
- To assess the impact of PRRT with lutetium (177Lu) edotreotide on trial patient’s HRQL and neuroendocrine functional tumor symptoms during and after therapy in comparison to best standard of care.(Heath Related Quality of Life (HRQL) questionnaires will be completed by the patient at randomization (D0) and then every 12± 2 weeks until adequately documented disease progression.)
- To assess the safety and tolerability of PRRT with lutetium (177Lu) edotreotide in trial patients compared to control treatment options.(Safety and tolerability based on AEs, laboratory data and vital signs will be assessed. AEs from signature of informed consent up to the patient experiencing a documented disease progression.)
- To assess the association of clinical/radiological outcomes with baseline characteristics, functional images and tumor gene profiling(Association of clinical/radiological outcomes with baseline characteristics, functional images and tumor gene profiling.)
- Endpoints based on RECIST v1.1,(Objective response rate (ORR), proportion of randomized patients with complete response (CR) or partial response (PR). Overall survival (OS), the time from randomization until death.)
研究者
研究点 (3)
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