NCT03753919终止2 期
A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for the Treatment of Patients With Progressive, Refractory Advanced Thyroid Carcinoma - The DUTHY Trial
Grupo Espanol de Tumores Neuroendocrinos15 个研究点 分布在 1 个国家目标入组 79 人开始时间: 2019年4月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 79
- 试验地点
- 15
- 主要终点
- Progression-free Survival Rate at 6 Months
研究概览
简要总结
This is a prospective, multi-centre, open label, stratified, exploratory phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in different cohorts of patients with thyroid cancers.
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
- •Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- •Age ≥ 18 years at time of study entry.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Body weight >30kg.
- •Confirmed differentiated thyroid cancer (papillary, follicular, poorly differentiated and Hürthle cell), medullary thyroid cancer and anaplastic thyroid cancer.
- •Available tumor and blood samples for translational research
- •Patients should meet one of the following criteria:
- •Cohort 1: Patients with locally advanced or metastatic differentiated thyroid cancer (including the subtypes of papillary, follicular, poorly differentiated and Hürthle cell carcinoma) after disease progression on systemic therapy with MKIs. Patients could be recruited in the study after progression on Lenvatinib (regardless prior lines) or progression on at least two prior MKIs which may or not include Lenvatinib. No prior therapy with immune check point inhibitors is allowed. Patients with intolerable toxicity to MKIs that meet the prior inclusion criteria and experience disease progression by RECIST v1.1 after stopping therapy may be included.
- •Cohort 2: Patients with locally advanced or metastatic medullary thyroid cancer after progression on systemic therapy with MKIs. Patients could be recruited in the study after progression to Vandetanib (regardless prior lines) or progression to at least two prior MKIs that may or not include Vandetanib. No prior therapy with immune check point inhibitors is allowed. Patients with intolerable toxicity to MKIs that meet the prior inclusion criteria and experience disease progression by RECIST v1.1 after stopping therapy may be included.
- •Cohort 3: Patients with locally advanced or metastatic anaplastic thyroid cancer regardless of prior therapy. No prior therapy with immune check point inhibitors is allowed.
- •No limitation of number of prior therapies.
- •Life expectancy >3 months
- •Adequate normal organ and marrow function as defined below: a) Haemoglobin ≥9.0 g/dL. b) Absolute neutrophil count (ANC) > 1500 per mm
- •c) Platelet count ≥100,000 per mm
- •d) Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. e) AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal. f) Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
- •Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: a) Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). b) Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- •Patient is 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.
排除标准
- •Participation in another clinical study with an investigational product during the last 21 days.
- •Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- •Any previous treatment with a PD1, PD-L1 or CTLA-4 inhibitor, including durvalumab and tremelimumab.
- •Any previous treatment with immunotherapy, including combinations of immunotherapy and other anticancer or targeted agents.
- •Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection). b) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. c) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: a) Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. b) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
- •Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- •History of allogenic organ transplantation.
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: a) Patients with vitiligo or alopecia. b) Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. c) Any chronic skin condition that does not require systemic therapy. d) Patients without active disease in the last 5 years may be included but only after consultation with the study physician. e) Patients with celiac disease controlled by diet alone.
- •Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- •History of another primary malignancy except for: a) Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence. b) Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease. c) Adequately treated carcinoma in situ without evidence of disease.
- •History of active primary immunodeficiency.
- •Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 90 days after the last dose of durvalumab monotherapy and 180 days for combined treatment with durvalumab and tremelimumab.
- •Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- •Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
研究组 & 干预措施
Durvalumab + Tremelimumab
Experimental
Durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks up to 4 cycles followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patients' decision.
干预措施: Durvalumab (Drug)
Durvalumab + Tremelimumab
Experimental
Durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks up to 4 cycles followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patients' decision.
干预措施: Tremelimumab (Drug)
结局指标
主要结局
Progression-free Survival Rate at 6 Months
时间窗: Throughout the study period, up to 6 months from start of treatment
6-months progression-free survival by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at 24 weeks after durvalumab plus tremelimumab was started without observing disease progression or death at this time point. Per RECIST for target lesions, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression disease. For non-target lesions, CR: Disappearance of all non-target lesions; Non-CR/Non-PD: Persistence of one or more non-target lesion(s).
Overall Survival Rate at 6 Months
时间窗: Throughout the trial period, up to 6 months from first dose of treatment.
Defined as percentage of patients alive at month 6 from first dose of treatment.
次要结局
- Overall Survival, Median(Throughout the trial period, with a following up to 4 years from the start of treatment)
- Overall Survival Rate at 18 Months(Throughout the trial period, up to 18 months from first dose of treatment.)
- Progression-free Survival (PFS), Median(Throughout the trial period, a median follow-up period 14 months from the start of treatment)
- Progression-free Survival Rate at 18 Months(Throughout the study period, up to 18 months from start of treatment)
- Overall Response Rate (ORR)(Through study completion, average 1 year)
- Overall Response (OR) Best Response According to RECIST 1.1(Throughout the trial period, with a following up to 4 years from the start of treatment)
- Overall Response (OR) Best Response According irRecist Criteria(Throughout the trial period, with a following up to 4 years from the start of treatment)
- Duration of Response (DoR) Median RECIST 1.1 Criteria(Through study period, assessed up to 4 years)
- Duration of Response (DoR) Median irRECIST Criteria(Through study period, assessed up to 4 years)
- Percentage of Participants With Treatment-Related Adverse Events (TRAEs)(Throughout the study period, from start treatment up 90 days after the last dose, up to 5 years.)
研究者
研究点 (15)
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