scholarly journals Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

2016 ◽  
Vol Volume 8 ◽  
pp. 323-333 ◽  
Author(s):  
Gabriel Tremblay ◽  
Christopher Livings ◽  
Lydia Crowe ◽  
Venediktos Kapetanakis ◽  
Andrew Briggs
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Thyroid Cancer ◽  
Survival Data ◽  
Differentiated Thyroid Cancer ◽  
Controlled Clinical Trial

scholarly journals Extended single-dose toxicity study of [211At]NaAt in mice for the first-in-human clinical trial of targeted alpha therapy for differentiated thyroid cancer

2021 ◽  
Author(s):  
Tadashi Watabe ◽  
Kazuko Kaneda-Nakashima ◽  
Kazuhiro Ooe ◽  
Yuwei Liu ◽  
Kenta Kurimoto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Thyroid Cancer ◽  
Single Dose ◽  
General Condition ◽  
Blood Test ◽  
Differentiated Thyroid Cancer ◽  
Targeted Alpha Therapy ◽  
Evaluation Point ◽  
Alpha Therapy

Abstract Objective Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [211At]NaAt to determine the FIH dose. Methods [211At]NaAt solution was injected into normal 6-week-old mice (male (n = 50) and female (n = 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (n = 20), 20 MBq/kg (n = 20), 50 MBq/kg (n = 30), saline control (n = 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity: n = 80) or 14 days (n = 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups. Results No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of [211At]NaAt. Conclusions In the extended single-dose toxicity study of [211At]NaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.

scholarly journals Prophylactic prednisolone for the prevention of early and intermediate adverse effects of radioactive iodine therapy in patients with thyroid cancer: study protocol for a single-centre, phase II/III, randomized, double-blinded, placebo-controlled clinical trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Umesh Jayarajah ◽  
Mahilal Wijekoon ◽  
Sanjeewa A. Seneviratne
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Thyroid Cancer ◽  
Adverse Effects ◽  
Differentiated Thyroid Cancer ◽  
Radioactive Iodine ◽  
Oral Prednisolone ◽  
Single Centre ◽  
Double Blinded

Abstract Background Radioactive iodine (RAI) therapy is the standard adjuvant treatment for differentiated thyroid cancer (i.e. papillary and follicular). RAI is associated with troublesome early, intermediate and late adverse effects. Although glucocorticoids are used for the management of these adverse effects, there is little evidence regarding the effectiveness of prophylactic glucocorticoids to prevent these complications. This trial will evaluate the efficacy of a short course of prophylactic glucocorticoids in the prevention of adverse effects of RAI treatment in patients with differentiated thyroid cancer. Methods A phase II/III, single-centre, randomized, double-blinded, placebo-controlled, parallel-arm clinical trial will be conducted. Patients with differentiated thyroid cancer who are referred to RAI therapy at the National Cancer Institute, Sri Lanka, will be randomized into two arms consisting of 200 patients each. The experimental group will receive prophylactic oral prednisolone 0.5 mg/kg and omeprazole 20 mg single dose 6 h before RAI therapy followed by oral prednisolone 0.5 mg/kg and omeprazole 20 mg daily for 3 days. The control group will receive oral placebo and omeprazole 20 mg single dose 6 h before RAI therapy followed by oral placebo and omeprazole 20 mg daily for 3 days. Clinically significant adverse effects assessed as related to RAI as well as prednisolone therapy and the quality of life parameters will be compared between the two groups. Discussion If proven beneficial, this intervention can be incorporated into the standard practice to reduce early and intermediate adverse effects of RAI for thyroid cancer with a potential improvement of quality of life. Trial registration Sri Lanka Clinical Trials Registry SLCTR/2020/009. Registered prospectively on 23 February 2020. Items of the WHO Trial Registration Data Set are provided in the supplementary file.

DOES T STAGE AFFECT PROGNOSIS IN PATIENTS WITH STAGE IV B DIFFERENTIATED THYROID CANCER?

2019 ◽  
Vol 25 (9) ◽  
pp. 877-886 ◽  
Author(s):  
Mu Li ◽  
Nitin Trivedi ◽  
Chenyang Dai ◽  
Rui Mao ◽  
Yuning Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Papillary Thyroid ◽  
Follicular Thyroid Cancer ◽  
Cancer Specific Survival ◽  
T Stage

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T [primary tumor size], N [regional lymph nodes], M [distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival. Methods: DTC cases that were considered stage IV B in the AJCC 8th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6th standard) was categorized into T0–2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis. Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS. Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary. Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database

Multi-center phase II/III randomized controlled clinical trial using TNFerade combined with chemoradiation in patients with locally advanced pancreatic cancer (LAPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4518-4518 ◽  
Author(s):  
M. Posner ◽  
K. J. Chang ◽  
A. Rosemurgy ◽  
J. Stephenson ◽  
M. Khan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Phase Ii ◽  
Dose Escalation ◽  
Survival Data ◽  
Interim Analysis ◽  
Dose Escalation Study ◽  
Absolute Increase ◽  
Ct Guided

4518 Background: TNFerade is a replication-deficient adenoviral vector carrying the transgene for human TNF-a protein, regulated by the radiation-inducible promoter Egr-1. A 50 patient (pt) phase II dose-escalation study in LAPC showed a possible dose-dependent improvement in survival. To confirm these findings, the randomized Pancreatic Cancer Clinical Trial with TNFerade (PACT) study was developed. PACT is a 330 pt study, powered to detect a 20% absolute increase in the primary efficacy endpoint (overall survival at 1 year) compared to standard of care (SOC) chemoradiation. An interim analysis of safety and efficacy was planned after the first 51 pts were randomized. Survival data to 11/15/06 has been evaluated and are reported here. Methods: The TNFerade arm pts received a five- wk treatment of weekly injections of 4 x 1011 pu TNFerade, continuous infusion 5-FU (200 mg/m2/day x 5 days/wk) and 50.4 Gy radiation. TNFerade was administered by percutaneous CT-guided transabdominal injection. The SOC arm received the same regimen, without TNFerade injections. Patients were randomized 2:1 to the TNFerade and SOC arms. The first 51 randomized pts were assessed for evidence of objective response (OR) and overall survival Results: Assessment of response data is still ongoing. TNFerade + SOC was well tolerated. One year survival, the primary endpoint of the study, was 70.5% in the TNFerade + SOC arm versus 28.0% in the SOC arm, an absolute increase of 42.5%. The median survival for TNFerade + SOC pts was 515 days compared to 335 days for the SOC pts. The logrank statistic for comparison between the two arms is X2 = 2.014 (p=0.16). Conclusions: The interim survival data is preliminary. The magnitude of the difference in survival in favor of the TNFerade + SOC arm, however, is encouraging. The data appears to corroborate previous findings from the dose-escalation study, which showed an apparent survival advantage in the 4×1011 pu dose group compared to 4 x 109 pu group. A second interim analysis is planned with larger patient numbers to determine whether this early positive trend is confirmed. No significant financial relationships to disclose.

Encorafenib and binimetinib with or without nivolumab in treating patients with metastatic radioiodine refractory BRAF V600 mutant thyroid cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS6085-TPS6085
Author(s):  
Matthew H. Taylor ◽  
Rom S. Leidner ◽  
Richard Bryan Bell ◽  
Bernard Fox ◽  
Hong Xiao ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Braf V600e ◽  
Braf Inhibitors ◽  
Multikinase Inhibitors ◽  
Braf Mutant

TPS6085 Background: Differentiated thyroid cancer is the most common endocrine malignancy and has a high frequency of actionable molecular aberrations including BRAF V600E mutations (45%), RET fusions (10%), and NTRK fusions ( < 2%). FDA approved systemic therapies for metastatic radioiodine refractory differentiated thyroid cancer (RR-DTC) include multikinase inhibitors (Lenvatinib and sorafenib), NTRK inhibitors (larotrectinib and entrectinib for NTRK fusion+ cancers), and RET inhibitors (selpercatinib and pralsetinib for RET fusion+ cancers). Previous phase II clinical trials showed clinical efficacy with first and second generation BRAF inhibitors in patients with BRAF mutant RR-DTC. BRAF inhibitors have not yet been FDA approved for treatment of BRAF mutant RR-DTC. Effective therapeutic options for patients with BRAF mutant RR-DTC remains an important unmet clinical need. BRAF mutant thyroid cancers often show elevated expression of PD-L1. Additionally, BRAF inhibition results in increased expression of PD-L1 in thyroid cancer. This clinical trial seeks to evaluate the safety and efficacy of encorafenib plus binimetinib with or without nivolumab in patients with BRAF mutant metastatic RR-DTC. Encorafenib and binimetinib are highly selective and potent oral inhibitors of BRAF and MEK, respectively. Nivolumab is a potent inhibitor of the immune co-inhibitory receptor programmed cell death protein 1 (PD-1). Methods: This is a phase II, single institution, open-label, randomized clinical trial evaluating the combinations of (Arm 1) encorafenib 450 mg/day + binimetinib 45 mg twice daily and (Arm 2) encorafenib 450 mg/day + binimetinib 45 mg twice daily + nivolumab 480 mg I.V. every 4 weeks in patients with metastatic BRAF mutant RR-DTC. The trial will enroll 20 patients in each arm and treatment will be given in 28 day cycles for up to 2 years. Eligible patients must have metastatic/unresectable BRAF mutant RR-DTC, an ECOG performance status of 0-1 and adequate bone marrow, liver and kidney function. Patients with CNS metastases are included if the metastases have been treated and remained stable or are asymptomatic and ≤10 mm in diameter. Patients may be systemic therapy naïve or have previously been treated with multikinase inhibitors. Prior therapy with BRAF, MEK or immune checkpoint inhibitors is exclusionary. The primary endpoint is confirmed objective response rate (ORR) determined by RECIST v1.1 with restaging imaging every 12 weeks. Secondary endpoints include progression free survival, overall survival, and safety/tolerability (CTCAE v5.0). Arms 1 and 2 will be evaluated independently and are not powered for direct comparison. The trial design includes continuous toxicity monitoring with a Pocock-type stopping boundary. This clinical trial is in progress and 3 patients have been enrolled. Clinical trial information: NCT04061980.

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