A randomized phase II study of pembrolizumab with or without radiation in patients with recurrent or metastatic adenoid cystic carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6082-6082 ◽  
Author(s):  
Jonathan Daniel Schoenfeld ◽  
Umair Mahmood ◽  
Yu-Hui Chen ◽  
Raymond H. Mak ◽  
Jochen H. Lorch ◽  
...  
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Phase Ii ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Distant Recurrence ◽  
High Rate ◽  
Tumor Growth Rate ◽  
Adenoid Cystic ◽  
Immune Biomarkers

6082 Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy characterized by a high rate of distant recurrence. Systemic therapy has generally failed to produce durable benefit. Radiation (RT) is used for localized disease and as directed treatment for metastases. Here, we report the safety and efficacy of pembrolizumab (pembro) administered with or without hypofractionated RT in a phase II randomized study. Methods: Eligible patients (pts) had recurrent or metastatic ACC with evidence of progressive disease (PD) within the last 12 mos and >=1 measurable non-CNS lesion, along with 1-5 additional lesions deemed appropriate for RT to 30 Gy in 5 fractions. Pts were randomized to pembro alone (200 mg IV q3 weeks) or in combination with RT given within 7 days of cycle 1, day 1. The primary endpoint was objective response rate (ORR) outside the RT field by RECIST 1.1. Using a parallel two-stage design, if >=1 response out of 10 was observed in either arm, 10 more pts would be enrolled to that arm. If >=3 responded, the null hypothesis (ORR=5%) would be rejected in favor of a 25% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses of tumor growth rate (TGR) excluding RT lesions and immune biomarkers were exploratory. Results: Ten pts per arm were randomized into the trial’s first stage with median age 65 (45-79). No objective responses were seen. Stable disease (SD) was observed in 13 pts; 6 had PD as best response, 1 was unevaluable. Median PFS was 7 mos 95% CI (3 - 13 mos), with 9 pts without progression at 6 mos. 3 pts remain on study treatment (range 8-11 mos). In pts with SD, TGR decreased by >25% in 7 of 12 pts and by >75% in 4 pts. There was no difference in likelihood of SD or PFS between arms. Treatment related AEs (TRAEs) occurred in 18 pts but there were no G3-5 TRAEs. Among 8 biopsies analyzed, PD-L1+ tumor/immune cells ranged from 12-52%. Conclusions: Pembro alone or with hypofractionated RT was well tolerated. We observed no objective responses, but 65% of pts with PD prior to study entry achieved SD, the majority with decreased TGR, and 15% had prolonged SD. Additional strategies are needed to further delay progression and effect response. Clinical trial information: NCT03087019.

scholarly journals Apatinib in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck: a single-arm, phase II prospective study

2021 ◽  
Vol 13 ◽  
pp. 175883592110136
Author(s):  
Guopei Zhu ◽  
Lin Zhang ◽  
Shengjin Dou ◽  
Rongrong Li ◽  
Jiang Li ◽  
...  
Keyword(s):  
Prospective Study ◽  
Adenoid Cystic Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Adenoid Cystic ◽  
Fatal Hemorrhage

Background: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. Methods: In this phase II single-arm, prospective study, patients aged 15–75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. Results: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% [95% confidence interval (CI): 83–97.5%], 75.2% (95% CI: 61.5–84.0%) and 44.7% (95% CI: 32.3–57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7–59.0%) and 98.5% (95% CI: 91.7–100.0%), respectively. The median duration of response was 17.7 months [interquartile range (IQR) 14.0–20.9]. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0–97.5%) and 82.3% (95% CI: 70–90.4%), respectively. The most common adverse events of grades 3–4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage. Conclusion: An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation. This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016)

Tumor Growth Rate as a Prognostic Factor for Metastatic or Recurrent Adenoid Cystic Carcinoma of the Head and Neck Patients Treated with Carboplatin Plus Paclitaxel

2020 ◽  
Author(s):  
Naoki Fukuda ◽  
Yu Fujiwara ◽  
Xiaofei Wang ◽  
Akihiro Ohmoto ◽  
Tetsuya Urasaki ◽  
...  
Keyword(s):  
Growth Rate ◽  
Prognostic Factors ◽  
Tumor Growth ◽  
Adenoid Cystic Carcinoma ◽  
Head And Neck ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Growth Rate ◽  
Adenoid Cystic ◽  
Exploratory Investigation

Abstract Background: Large prospective studies of chemotherapy for metastatic or recurrent adenoid cystic carcinoma (ACC) of the head and neck are lacking due to the rarity of ACC. The aim of this study is to evaluate the efficacy of carboplatin plus paclitaxel toward ACC and perform an exploratory investigation of the prognostic factors to investigate the optimal strategy for metastatic or recurrent ACC.Methods: We retrospectively analyzed recurrent or metastatic ACC patients treated with carboplatin plus paclitaxel between April 2007 and September 2019 in our hospital. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated, and an exploratory analysis of the prognostic factors including tumor growth rate (TGR) was conducted.Results: A total of 26 ACC patients were enrolled. ORR and DCR were 11.5% and 76.9%; the median PFS and OS were 8.1 and 22.3 months, respectively. From the results of the multivariate analysis, higher (≥ 6%/month) TGR was associated with worse PFS (hazard ratio [HR] 7.00, 95%CI 1.34–36.53, p = 0.02) and OS (HR 29.33, 95%CI 3.38–254.80, p < 0.01). The median PFS (10.6 vs. 6.6 months, log-rank p < 0.05) and OS (48.5 vs. 16.9 months, log-rank p < 0.01) were significantly shorter in patients with higher TGR.Conclusions: Carboplatin plus paclitaxel showed modest efficacy for recurrent or metastatic ACC patients. Watchful waiting may be optimal for ACC patients with lower TGR. Systemic chemotherapy should be considered when TGR increases during active surveillance.

Randomized phase II study of axitinib versus observation in patients with recurred or metastatic adenoid cystic carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6503-6503 ◽  
Author(s):  
Bhumsuk Keam ◽  
Eun Joo Kang ◽  
Myung-Ju Ahn ◽  
Chan-Young Ock ◽  
Keun Wook Lee ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Trial ◽  
Adenoid Cystic Carcinoma ◽  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Ii Trials ◽  
Adenoid Cystic ◽  
Observation Methods ◽  
Duration Of Response

6503 Background: Adenoid cystic carcinoma (ACC) does not respond to cytotoxic chemotherapy. Several anti-angiogenic agents were evaluated in single arm phase II trials. However, the role of chemotherapy is still controversial, because of natural stable disease course without chemotherapy and lack of randomized trial. We firstly conducted a randomized trial to evaluate the efficacy of axitinib compared to observation. Methods: In this multicenter, prospective phase II trial, we enrolled recurred, metastatic ACC patients who progressed within 9 months. Patients were randomly assigned either axitinib (5mg twice daily) or observation arm with 1:1 ratio. Crossover to the axitinib arm was permitted for patients in the observation arm who had disease progression. The primary endpoint was 6-month progression-free survival (PFS) rate. The secondary endpoints included objective response rate (ORR), overall survival (OS), PFS, duration of response and adverse events. Results: A total of 60 patients randomly allocated to axitinib (N=30) and observation arm (N=30) and response evaluation was conducted in 57 patients. With a median follow-up of 25.4 months, the 6-month PFS rate was 73.2% (95% confidence interval [CI], 54.8 to 88.1%) in the axitinib arm and 23.2% (95% CI, 9.3 to 41.1%) in the observation arm (hazard ratio, 0.19; 95% CI, 0.08 to 0.45; P < 0.001). Median PFS was 10.8 months in axitinib arm and 2.8 months in observation arm ( P < 0.001). The ORR was 3.3% (95% CI, 0.1 to 17.2%) in the axitinib arm, and 0% (95% CI, 0 to 12.8%) in the observation arm. The disease control rate was 100% (95% CI, 88.4 to 100%) in the axitinib arm and 51.9% (95% CI, 32.0 to 71.3%) in the observation arm. After crossover, ORR of axitinib in the observation arm was 11.1% (95% CI, 2.4 to 29.2%). Median OS was not reached in axitinib arm, 28.5 months in observation arm ( P = 0.688). The most frequently reported adverse events of axitinib were grade 1 or 2 oral mucositis and fatigue. Detailed data of adverse events and mutational profile data will be presented. Conclusions: In this first randomized trial in patients with recurred or metastatic ACC, axitinib significantly increased 6-month PFS rate compared to observation. Clinical trial information: NCT02859012 .

scholarly journals Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma

2019 ◽  
Vol 37 (18) ◽  
pp. 1529-1537 ◽  
Author(s):  
Vatche Tchekmedyian ◽  
Eric J. Sherman ◽  
Lara Dunn ◽  
Crystal Tran ◽  
Shrujal Baxi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Adenoid Cystic Carcinoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Overall Response ◽  
End Point ◽  
Adenoid Cystic

PURPOSE Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) is a malignant neoplasm of predominantly salivary gland origin for which effective therapies are lacking. We conducted a phase II trial evaluating the multitargeted tyrosine kinase inhibitor lenvatinib in patients with R/M ACC. PATIENTS AND METHODS This study was conducted with a two-stage minimax design. Patients with histologically confirmed R/M ACC of any primary site with radiographic and/or symptomatic progression were eligible. Any prior therapy was allowed except previous lenvatinib. Patients received lenvatinib 24 mg orally per day. The primary end point was overall response rate. Secondary end points were progression-free survival and safety. An exploratory analysis of how MYB expression and genomic alterations relate to outcomes was conducted. RESULTS Thirty-three patients were enrolled; 32 were evaluable for the primary end point. Five patients (15.6%) had a confirmed partial response, 24 patients (75%) had stable disease, two patients (6.3%) discontinued treatment as a result of toxicity before the first scan, and one patient (3.1%) had progression of disease as best response. Median progression-free survival time was 17.5 months (95% CI, 7.2 months to not reached), although only eight progression events were observed. Patients otherwise were removed for toxicity (n = 5), as a result of withdrawal of consent (n = 9), or at the treating physician’s discretion (n = 6). Twenty-three patients required at least one dose modification, and 18 of 32 patients discontinued lenvatinib for drug-related issues. The most common grade 3 or 4 adverse events were hypertension (n = 9; 28.1%) and oral pain (n = 3; 9.4%). Three grade 4 adverse events were observed (myocardial infarction, n = 1; posterior reversible encephalopathy syndrome, n = 1; and intracranial hemorrhage, n = 1). CONCLUSION This trial met the prespecified overall response rate primary end point, demonstrating antitumor activity with lenvatinib in R/M ACC patients. Toxicity was comparable to previous studies, requiring monitoring and management.

RAMSETE: A single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in Europe.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4122-4122 ◽  
Author(s):  
Marianne E. Pavel ◽  
Bertram Wiedenmann ◽  
Jaume Capdevila ◽  
Nicholas Reed ◽  
Juan W. Valle ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Rate ◽  
Mucosal Inflammation ◽  
Duration Of Treatment ◽  
Open Label ◽  
Best Response

4122 Background: The mammalian target of rapamycin (mTOR) signaling pathway is involved in the pathogenesis of neuroendocrine tumors (NET). Everolimus (RAD001), an oral mTOR inhibitor, has antitumor activity in patients (pts) with advanced NET. In this open-label, multicenter, phase II study (RAMSETE), the safety and efficacy of everolimus monotherapy was evaluated in pts with advanced nonsyndromic, nonpancreatic NET. Methods: Pts with advanced (unresectable or metastatic), progressive, nonsyndromic, nonpancreatic NET received everolimus (10 mg/day) as monotherapy. The primary endpoint was objective response rate (proportion of pts with best overall complete response [CR] or partial response [PR] per RECIST v1.0) by central radiologic review. A secondary endpoint included progression-free survival (PFS). Results: By database soft lock (December 1, 2011), 73 pts from 16 European clinics received everolimus (median duration of treatment: 193 days). Fifty-five (75%) pts discontinued; reasons included disease progression (n=23), adverse events (AEs [n=23]), withdrawal of consent (n=4), death (n=3), and protocol deviation (n=2). In the per protocol population (N=60), 32 (53%) pts received prior antineoplastic therapy. The best response by central review was stable disease in 55%. By local review, 3 (5%) pts had a PR, with SD in 39 (65%) pts. Median PFS by central review was 185 days (95% CI: 158-255). Median PFS by local investigator review was 285 days (95% CI: 231-not estimable). 69 (95%) pts reported treatment-related AEs of any grade, including rash (n=28; 38%), diarrhea (n=20; 27%), mucosal inflammation (n=18; 25%), and decreased appetite (n=17; 23%). Treatment-related grades 3 and 4 AEs and serious AEs were reported by 27 (37%) and 18 (25%) pts, respectively. Conclusions: In this open-label trial of everolimus in pts with advanced, nonsyndromic, extrapancreatic NET, a high rate of disease stabilization was achieved after prior tumor progression with favorable median PFS. This study further supports efficacy of everolimus in types of NET other than those studied in RADIANT-3 (pancreatic NET) and RADIANT-2 (NET associated with carcinoid syndrome).

Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Extended follow-up on the multicenter, single-arm phase II ORIENT-1 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7533-7533
Author(s):  
Hang Su ◽  
Yongping Song ◽  
Wenqi Jiang ◽  
Xiuhua Sun ◽  
Wenbin Qian ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Rate ◽  
Hodgkin's Lymphoma ◽  
Primary Analysis ◽  
Hematopoietic Stem

7533 Background: Classical Hodgkin’s lymphoma (cHL) is characterized by chromosome 9p24.1 alterations and PD-1 ligand overexpression. Sintilimab, a programmed death-1 checkpoint inhibitor, has demonstrated efficacy in relapsed/refractory cHL after the primary analysis of the ORIENT-1 study. Here, we report the updated safety and efficacy prolines after extended follow-up. Methods: ORIENT-1 is a multicenter, single-arm, phase II study in China. Classical Hodgkin’s lymphoma patients who had failed ≥2 lines of systemic therapy, including autologous hematopoietic stem cell transplantation (HSCT) were enrolled. Sintilimab, 200 mg IV was given every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee (IRRC) according to 2007 IWG criteria. Results: 96 patients were treated. As of the data cutoff on 16 October, 2018 72.9% of patients were continuing treatment with a median follow-up of 14 months. Median number of treatment cycles was 20 (range: 1 to 26). ORR was 85.4% (82/96, 95%CI: 76.7 to 91.8) based on IRRC review. Twenty-eight patients (29.2%) achieved complete response (CR) by PET scan. At the time of analysis, 59 out of 82 patients who had achieved complete or partial response continued to have an on-going response. The median duration of response (DoR) and progression free survival (PFS) have not been reached. The most common treatment-related adverse event (TRAE) was pyrexia (40.6%, 39/96), 92.3% of which was grade 1 or 2. The most common grade 3 or 4 TRAEs were pyrexia (3.1%) and anemia (3.1%). One death occurred which was not considered treatment related. Conclusions: ORIENT-1 study has the largest cohort of cHL patients in China treated with a PD-1. In addition to a high rate of response, sintilimab also demonstrated durable efficacy and favorable long-term safety profile after extended follow-up. Clinical trial information: NCT03114683.

Amrubicin and carboplatin with pegfilgrastim in patients with extensive-stage small-cell lung cancer (ES-SCLC): A phase II study of the Sarah Cannon Research Institute (SCRI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7100-7100
Author(s):  
Dianna Shipley ◽  
John D. Hainsworth ◽  
Tarek Mekhail ◽  
John D. Zubkus ◽  
Douglas B. Flora ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Highly Active ◽  
Impact On Survival ◽  
Elderly Japanese ◽  
Ecog Ps

7100 Background: Amrubicin is a novel anthracycline associated with high objective response rates (ORR) in patients (pts) with relapsed SCLC. Amrubicin improved the ORR and progression-free survival (PFS) in relapsed SCLC vs. topotecan, but not overall survival (OS) in a phase III study. Amrubicin with cisplatin/carboplatin for elderly Japanese pts was safe and active. We conducted a multicenter phase II study evaluating amrubicin and carboplatin in newly diagnosed ES-SCLC. Methods: Eligible pts had untreated ES-SCLC, measurable/evaluable disease (RECIST v. 1.1) and an ECOG PS <2. Pts received 4 cycles of amrubicin 30 mg/m2 on days 1-3 and carboplatin AUC=5 both IV day 1 every 21 days with restaging every 6 weeks. Pegfilgrastim 6 mg sq was administered on day 4 of each cycle. The primary endpoint was 1-year OS. Secondary endpoints included ORR, PFS, OS, and toxicity. Results: 78 pts were enrolled from 3/2010 to 7/2011. Baseline characteristics included: median age 65 yrs (range 45-84); 56% female. 64% completed 4 cycles of treatment. Eleven (14%) pts showed complete responses and 47 (60%) pts partial responses, for an ORR of 74% (95% confidence interval 65%-82%). Twelve (15%) pts had stable disease. Median PFS and OS were 5.3 and 9.5 months, respectively. The 1-year OS was 36%. Grade 3/4 myelosuppression was the most common toxicity (thrombocytopenia 44%, neutropenia 34%, febrile neutropenia 12%, anemia 26%), but was manageable. Severe non-hematologic toxicities (>5%) included hypokalemia 17%, fatigue 13%, dehydration 10%, hyponatremia 10%, pneumonia 9%, and nausea/vomiting 8%. 1 pt died from sepsis and another from aspiration pneumonia. Conclusions: First-line ES-SCLC treatment with amrubicin and carboplatin induced several complete responses and is considered highly active. Myelosuppression was managed effectively with growth factor support. These results are comparable to historical data with platinum-doublet chemotherapy. A larger randomized study would be required to best assess this regimen’s impact on survival.

Phase II study of dovitinib (TKI258) in patients with progressive metastatic adenoid cystic carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6021-6021 ◽  
Author(s):  
Patrick Michael Dillon ◽  
Chris Moskaluk ◽  
Paula M. Fracasso ◽  
Gina R. Petroni ◽  
Christopher Y. Thomas
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Kinase Inhibitor ◽  
Lung Metastases ◽  
Objective Response ◽  
Tumor Growth Rate ◽  
Type I ◽  
Duration Of Treatment ◽  
Open Label ◽  
Adenoid Cystic ◽  
Stomach Pain

6021 Background: Adenoid cystic carcinoma (ACC) is an uncommon malignancy of secretory glands for which there is no standard systemic therapy. At least 90% of ACC tumors carry a t(6;9)(q22–23;p23–24) chromosome translocation that results in overexpression of the MYB oncogene that in turn upregulates FGF2 and other growth factors. Dovitinib is a multiple receptor kinase inhibitor that could potentially block autocrine activation of the FGFR and VEGFR-mediated angiogenesis. In a mouse model, dovitinib suppressed the growth of low passage ACC xenografts. Methods: In this open-label, single-arm trial, patients (n=21) with metastatic ACC that progressed in the last 6 months were treated with dovitinib 500 mg/d, 5-days on/2-days off. The primary endpoint was objective response rate using a two-stage design to test a null and alternative rate of 1% and 18%, respectively, with 90% power and type I error <5%. Secondary endpoints were progression-free survival, safety, quality of life, biomarker studies, and change in tumor growth rate. Results: All 21 patients (median age 54.3, range 29-74) had previous treatment with chemotherapy, radiotherapy or targeted agents. Median duration of treatment to date is 5.7 months (range 2-10 months) and is ongoing in 11 patients. Nine of 21 patients required dose reductions. Grade 3/4 drug-related adverse events included thromboembolism (4), hematuria (1), dehydration (1), pneumonia (2), hypertriglyceridemia (3), diarrhea (2), stomach pain (2), anxiety (1), transaminitis (3) and cytopenias (4). One death occurred unrelated to study drug. Among 19 evaluable patients, 2 had partial responses by RECIST criteria (1 with lung metastases and 1 with tracheal recurrence and stable bone metastases). Both experienced improvements in pain ratings and are free of disease progression at 8+ and 5+ months. Stable disease >6 months was observed in 9 patients while 6 others with shorter follow-up have not progressed. Four patients progressed early (<4 months) and two are too early to assess. Conclusions: Dovitinib produces objective partial responses and prolonged tumor stabilization with acceptable toxicity in patients with progressive ACC. Clinical trial information: NCT01524692.

A phase II, randomized, controlled trial of nivolumab in combination with BMS-986253 or cabiralizumab in advanced hepatocellular carcinoma (HCC) patients.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS598-TPS598
Author(s):  
Theodore Welling ◽  
Nina Beri ◽  
Despina Siolas ◽  
Deirdre Jill Cohen ◽  
Daniel Jacob Becker ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitors ◽  
Controlled Trial ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response Rates ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

TPS598 Background: Tyrosine kinase inhibitors can prolong survival in advanced HCC patients, but response rates have been minimal. Recently, immune checkpoint inhibition with nivolumab (nivo) demonstrated objective response rates (ORR) of 15% (escalation phase) and 20% (expansion phase) in the Checkmate 040 study. Pre-clinical and translational studies have demonstrated that IL-8 and tumor associated macrophages (TAMs) contribute to HCC progression and recurrence following treatment. Therefore, rationale exists to evaluate combinatorial approaches to target TAM function combined with checkpoint inhibitory therapy. This phase II, randomized study will evaluate the safety and efficacy of combined anti-CSF1R (Cabiralizumab) or anti-IL-8 (BMS-986253) in combination with Nivo in advanced HCC. Methods: Advanced HCC patients without prior systemic treatment and disease measurable by RECISTv1.1 with Childs A liver function are eligible. Patients will be enrolled (n=25 per arm) to Nivo 240 mg IV Q2 weeks monotherapy, Nivo 240 mg IV + BMS-986253 1200 mg IV Q2 weeks, or Nivo 240 mg IV + Cabiralizumab 4 mg/kg IV Q2 weeks. Primary endpoints include safety and ORR determined by RECISTv1.1. Secondary endpoints include time to response, duration of response, progression free survival, and overall survival. Exploratory endpoints include analysis of tumor microenvironment immune and tumor cell profiling of pre- and on-treatment tumor tissue. Clinical trial information: NCT04050462.

TCOG T5217 trial: A phase II randomized study of SLOG versus modified FOLFIRINOX as the first-line treatment in locally advanced or metastatic pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4143-4143
Author(s):  
Nai-Jung Chiang ◽  
Yan-Shen Shan ◽  
Li-Yuan Bai ◽  
Chung-Pin Li ◽  
Jen-Shi Chen ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Phase Ii ◽  
Randomized Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
First Line ◽  
Fixed Rate ◽  
Disease Extent

4143 Background: The triplet regimen of S-1, leucovorin, oxaliplatin and gemcitabine (SLOG) has shown promising efficacy for metastatic pancreatic ductal adenocarcinoma (PDAC) in our previous study. Current multicenter randomized, phase II study compared the efficacy and safety of SLOG versus modified FOLFIRINOX (mFOLFIRINOX) in patients with advanced/metastatic PDAC. Methods: Patients with chemo-naïve, histologically confirmed advanced/metastatic PDAC, were randomly assigned to either SLOG (gemcitabine 800 mg/m2, fixed-rate infusion and oxaliplatin 85 mg/m2 on day 1, plus daily 40/50/60 mg of S-1 based on BSA and 30 mg of oral leucovorin, twice daily, on days 1-7, every 2 weeks) or mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2 and leucovorin 400 mg/m2 on day 1 plus 5-FU 2400 mg/m2 for 46 hrs, every 2 weeks). Patients were stratified according to disease extent, ECOG PS and primary tumor location. The primary endpoint was 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, and overall survival (OS) and safety profile. Tumor response was assessed by CT/MRI every 8 weeks according to RECIST v1.1. As an exploratory trial, 130 (65 per arm) patients were estimated to detect a two-sided 15% difference in 6-month PFS (60% in SLOG and 45% in mFOLFIRINOX) with a significant level of α = 0.1 and β = 0.25. Results: Between March 2018 and October 2019, 130 patients were accrued. One patient who was assigned to mFOLFIRINOX arm didn’t receive assigned treatment. Of them, 62.3% were male, 45.4% were ECOG PS0, 81.5% had metastatic diseases, and 16.9% had prior surgery. The 6-month PFS rate was 55.4% in SLOG arm (n = 65) and 50% in mFOLFIRINOX arm (n = 64) (p = 0.850). The ORR and DCR in the SLOG and the mFOLFIRINOX arms were 40% versus 26.6% (p = 0.135) and 76.2% versus 71.9% (p = 0.550), respectively. The median PFS was 7.5 months in SLOG arm and 6.5 months in mFOLFIRINOX arm (p = 0.395); while the median OS was 12.9 months in SLOG arm and 12.1 months in mFOLFIRINOX arm (p = 0.88). Ten patients underwent conversion surgery, of whom 7 had SLOG and 3 had mFOLFIRINOX. The incidence of grade 3/4 neutropenia was significantly higher in mFOLFIRINOX arm (53.2% vs. 16.9% in SLOG arm, p < 0.0001). Conclusions: SLOG could achieve comparable but numerically better ORR, and median PFS and OS as compared to mFOLFIRINOX in patients of advanced PDAC. SLOG can be an alternative first-line regimen for advanced PDAC patients. Clinical trial information: NCT03443492.

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