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2019年4月2日

适应症Metastatic Thyroid Papillary Carcinoma Metastatic Thyroid Follicular Carcinoma Metastatic Thyroid Cancer

干预措施Durvalumab Tremelimumab

概览

阶段: 2 期
干预措施: Durvalumab
疾病 / 适应症: Metastatic Thyroid Papillary Carcinoma
发起方: Grupo Espanol de Tumores Neuroendocrinos
入组人数: 79
试验地点: 15
主要终点: Progression-free Survival Rate at 6 Months
状态: 终止
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

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.

注册库

clinicaltrials.gov

开始日期

2019年4月2日

结束日期

2024年11月8日

最后更新

上个月

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Grupo Espanol de Tumores Neuroendocrinos

责任方

Sponsor

入排标准

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.

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.

研究组 & 干预措施

Durvalumab + Tremelimumab

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

Durvalumab + Tremelimumab

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

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.)