scholarly journals PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Julia E. Douglas ◽  
Suyu Liu ◽  
Junsheng Ma ◽  
Robert A. Wolff ◽  
Shubham Pant ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Phase Iii ◽  
Cancer Center ◽  
Phase Ii Trials ◽  
Treatment History

Abstract Background Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need. Methods This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated. Discussion To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease. Trial registration This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204.

Witnessing a New Era? – The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2010 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signalling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomised Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarise the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Witnessing a New Era?—The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2012 ◽  
Vol 08 (02) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signaling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomized Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarize the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

A pooled analysis of phase II trials of gemcitabine (GEM)-containing doublets plus bevacizumab (BEV):  Should combination chemotherapy serve as the backbone in clinical trials of advanced pancreatic cancer (APC)?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4038-4038
Author(s):  
Katherine Van Loon ◽  
George P. Kim ◽  
Anne Marie Espinoza ◽  
David R. Fogelman ◽  
Renuka V. Iyer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase Ii ◽  
Trial Design ◽  
Bowel Perforation ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Cardiac Events ◽  
Phase Ii Trials ◽  
Grade 3

4038 Background: GEM has served as the chemotherapy platform for most phase III clinical trials in APC, inc. CALGB 80303 (GEM +/- BEV). However, GEM-based combination regimens may confer superior outcomes in select pts and represent a preferred backbone in clinical trial design testing targeted agents. Methods: Data was pooled from 5 phase II trials evaluating GEM-based cytotoxic doublets plus BEV in APC. 1o endpoint was OS. 2o endpoints included ORR, CA19-9 response, and adverse events (AEs). Kaplan-Meier methods estimated time-to-event endpoints. The Cox proportional hazard model estimated univariate hazard ratios (HR) of death. Results: Of 261 pts, 90.7% were Caucasian, 95.4% had an ECOG PS 0-1, and 91.6% had metastatic disease. Median age = 60y. Pooled OS data (in mos), stratified for PS and stage, is shown in the table. ORR across all trials: CR 1.6%, PR 22.9%, SD 50.8%, PD 20.2%, NA 4.7%. HR for pts who achieved disease control (CR/PR/SD) was 0.35 vs. those with PD (95% CI 0.23-0.54, p<0.001). 76.5% of pts had elevated baseline CA19-9; of these, 62% achieved ≥50% reduction (HR 0.50; 95% CI 0.34-0.73, p<0.001). BEV-related AEs ≥grade 3: HTN (10.6%), hemorrhage (9.5%), VTE (10.1%), cardiac events (3.4%), and bowel perforation (2.2%). Median OS in pts with grade 3-4 HTN was 13.4 mos vs. 9.8 mos in those without (HR 0.77; 95% CI 0.48-1.24, p=0.29). Conclusions: Recognizing the limitations of single-arm phase II trial design and cross-study comparisons, these results compare favorably to those from CALGB 80303. The standard paradigm of GEM +/- drug X in clinical trial development for APC needs to be reconsidered. Based on our data as well as the recent phase III FOLFIRINOX study, building on more intensive combination chemo regimens in future trials may represent a better strategy, especially for pts with good PS. [Table: see text]

Updated results of a randomized phase II trial for neoadjuvant versus adjuvant docetaxel/cisplatin chemotherapy in patients with locally advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 111-111
Author(s):  
Young Woo Kim ◽  
Keun Won Ryu ◽  
Il Ju Choi ◽  
Myeong-Cherl Kook ◽  
Young Iee Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Cancer Center ◽  
Locally Advanced Gastric Cancer ◽  
Randomized Phase Ii

111 Background: Recent phase III trials proved the role of adjuvant chemotherapy in patients with gastric cancer after D2 resection, but the optimal treatment sequence remains to be determined. Here we report long-term follow up results for the randomized phase II trial comparing between neoadjuvant and adjuvant docetaxel/cisplatin (DC) chemotherapy in patients with locally advanced gastric cancer (LAGC). Methods: Patients with LAGC (stage IIIA-IV) were stratified by Japanese staging system and randomized to either neoadjuvant or adjuvant weekly DC chemotherapy in the National Cancer Center of Korea from 2003 to 2005. FDG-PET/CT screening was employed to exclude patients with metastasis. Patients randomized to neoadjuvant arm received 3 cycles of DC regimen (docetaxel 36 mg/m2 and cisplatin 40 mg/m2 on days 1 and 8 every 3 weeks), followed by surgery (D2 dissection). In adjuvant arm, patients underwent surgery, followed by 3 cycles of the same DC chemotherapy regimen. Results: Neoadjuvant arm (n=43) demonstrated higher R0 resection rate than adjuvant arm (n=44) [81% v 73%], but the difference was not statistically significant. At a median follow-up for suriving patients of 7.2 years, there were no significant differences in OS and PFS between the two arms [Log rank P=0.93 and P=0.89, respectively]. Conclusions: The timing of perioperative DC chemotherapy does not affect the overall survival of patients with LAGC.

Clinical trial accrual rates in prostate cancer: Prospective experience from a single institution

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15611-15611
Author(s):  
N. J. Vogelzang ◽  
B. Wong ◽  
D. Pomerantz ◽  
K. L. Power ◽  
C. W. Adams ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase I ◽  
Data Base ◽  
Phase Ii ◽  
Cancer Registry ◽  
National Average ◽  
Phase Iii ◽  
Cancer Center ◽  
Screen Failure

15611 Background: Clinical trial (CT) participation is a key to better cancer therapy. The Nevada Cancer Institute (NVCI), the official cancer center of NV, is committed to CT participation. We hypothesized that CT accrual at the NVCI should exceed the national average of 3–5%. Methods: Patient (pt) visits began in 3/05 and by 12/31/07 1363 pts had been seen. Prostate cancer (PC) was the largest group (N=270; 50 with 1 visit only). All records are electronic and entered into a cancer registry. A relatively robust portfolio of PC CTs has been available, thus the cancer registry data base was compared to the CT data base for the 16 PC CTs (8 phase III, 1 phase II, 7 phase I) that accrued pts. The data base records all accruals, screen failures, consent withdrawals, and subsequent treatments (on or off CT). Results: 101 consents were signed by 68 PC pts (25 consented to 2 or more CTs). 31 consents lead to screen failures/consent withdrawal (5 pts were screen failures for 2 CTs while 1 pt was a screen failure for 3 CTs). Screen failure was less common in phase II/III CTs (18/74 =24%) than in phase I CTs (10/27=37%). Most of the phase I screen failures were due to rapid decreases in performance status or organ function dysfunction. Among the 68 unique pts who consented, 35 pts were treated on 1 CT and 16 pts were treated on 2 or more CTs resulting in a total of 51 PC pts being treated on at least 1 CT. Conclusions: CT accrual at the NVCI of PC pts (51/270=19%) exceeds the national average. Reports of CT activity should specify the denominator and include both consent and accrual rates. Screen failure/consent withdrawal was common in this older male population with advanced disease. This analysis has limitations; Phase I CTs were activated only after 10/05, only 1 phase II CT was open during this period and CTs for radiation and surgery alone for PC pts were not open. Thus, the percent of pts on CT should rise as more CTs are activated. No significant financial relationships to disclose.

Gemcitabine, paclitaxel, and doxorubicin as first-line therapy for patients with advanced urothelial carcinoma and renal insufficiency: A phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4528-4528 ◽  
Author(s):  
Lance C. Pagliaro ◽  
Mark F. Munsell ◽  
Deborah Harris ◽  
Robert L. Carolla ◽  
Arlene O. Siefker-Radtke
Keyword(s):  
Renal Insufficiency ◽  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Unmet Need ◽  
Phase Iii ◽  
First Line ◽  
Advanced Urothelial Carcinoma

4528 Background: The role of cisplatin-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma is well established. For patients (pts) who cannot receive cisplatin owing to renal insufficiency, substitution with carboplatin was associated with inferior response rate and overall survival (OS). To address this unmet need, we conducted a phase II study of gemcitabine (Gem), paclitaxel (Tax), and doxorubicin (Adria) in this group. Methods: The primary endpoint was overall response rate (ORR); secondary endpoints were toxicity, OS, and the safety and efficacy of pegfilgrastim 6 mg (G-CSF) given immediately after chemotherapy on Day 1. A Simon 2-stage design was chosen to detect ORR of 40% and to reject ORR of 25%. Eligible pts had metastatic or unresectable urothelial carcinoma, no prior chemotherapy, performance status ≤ 2, glomerular filtration < 60 ml/min, and no need for dialysis; all gave informed consent. Brain metastases were excluded, as were clinically significant heart disease, peripheral neuropathy, and liver or bone marrow dysfunction. Treatment consisted of 900 mg/m2 Gem (fixed rate of 10 mg/m2/min), 135 mg/m2 Tax, and 40 mg/m2 Adria administered with same-day GCSF every 14 d to a maximum of 9 cycles. Tumors were evaluated after every 3 cycles. Results: Forty pts were enrolled January 2008 through November 2011, and 39 could be assessed for response. Median age was 72 (range, 51–89) and 11 pts (28.2%) were women. There were 7 complete and 15 partial responses, for an ORR of 56.4% (95% CI 39.6-72.2). Notable grade 3 and 4 nonhematologic toxicities in the first 2 cycles were dyspnea and mucositis (1 pt each). There were no treatment-related deaths and no toxicity attributed to same-day G-CSF. Median OS was 14.4 mo with median follow-up of 12.6 mo for all pts, 15.6 mo for 10 who were alive. Conclusions: Gem-Tax-Adria is effective as first-line treatment for metastatic or locally advanced urothelial carcinoma, and it can safely be given to pts with renal insufficiency. Same-day G-CSF also appears to be safe and effective in this setting. Phase III study is warranted. Clinical trial information: NCT00478361.

A phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4027-4027 ◽  
Author(s):  
Min Hee Hong ◽  
HyeRyun Kim ◽  
Seong Yong Park ◽  
Dae Joon Kim ◽  
Chang Geol Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Primary Tumor ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii

4027 Background: Even though preoperative chemoradiotherapy (CRT) showed survival improvement in patients with resectable ESCC in a randomized trial over upfront surgery, ESCC still has a dismal prognosis. With the potential benefit of combining PD-1 blockade to CRT, we conducted a phase II trial which assessed the efficacy, feasibility, and safety of the combination of preoperative CRT and pembrolizumab (PEM) in ESCC. Methods: Patients (pts) with histologically confirmed ESCC (clinical stage Ib to III according to the American Joint Committee on Cancer 7th staging system) were enrolled. Pts received concurrent neoadjuvant chemotherapy (weekly paclitaxel and carboplatin), radiotherapy (44.1 Gy in 21 fractions), and PEM (every 3 week, 200 mg) during 5 weeks followed by surgery. After surgery, pts were treated with PEM during 2 years or until progression, unacceptable toxicity, death, or pts’ refusal, which came first. The primary endpoint was pathologic complete response (pCR) rate in the primary tumor and secondary endpoints were overall survival (OS), disease-free survival (DFS), the incidence of adverse events, and etc. Results: In a total of 28 enrolled pts (median age 60), 26 pts received esophagectomy. Two pts did not undergo surgery due to death (hematemesis) and consent withdrawal. There were two in-hospital mortality cases after surgery, which were resulted from acute lung injury. The pCR in primary tumor was achieved in 46.1% of pts who underwent resection (95% CI: 28.8 – 64.6). With a median follow-up of 11.7 months, median OS was not reached. Six-month and 12-month OS rates were 89.3% and 82.1%, respectively. There was a trend toward better DFS in the pCR group (n = 12) compared with the non-pCR group (n = 14) (HR = 0.33, p = 0.1). Most common treatment-related adverse events were neutropenia (50.0%) and liver enzyme elevation (30.8%) in the neoadjuvant and adjuvant period, respectively. Conclusions: The addition of PEM to preoperative CRT in ESCC demonstrated promising efficacy with acceptable toxicity. Based on the results, further investigation is warranted in a phase III clinical trial. The exploratory endpoints including biomarkers analyses are ongoing. Clinical trial information: NCT02844075.

A randomized phase II/III study of paclitaxel/cisplatin versus cisplatin/5-fluorouracil in neoadjuvant chemoradiotherapy (CRT) followed by surgery for patients with locally advanced esophageal squamous cell carcinoma (ESCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4650-TPS4650
Author(s):  
Ta-Chen Huang ◽  
Chih-Hung Hsu ◽  
Jason C. Cheng ◽  
Chia-Chi Lin ◽  
Jhe-Cyuan Guo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Phase Iii ◽  
Phase 2 ◽  
Significance Level

TPS4650 Background: Meta-analyses have shown the survival benefit of cisplatin/5-fluorouracil (PF) neoadjuvant CRT over surgery alone for patients with locally advanced ESCC. The CROSS study has demonstrated the statistically significant survival benefit of paclitaxel/carboplatin neoadjuvant CRT for patients with locally advanced esophageal cancer, especially ESCC. A network meta-analysis based on published phase III trials suggested that paclitaxel/platinum might be superior to PF as neoadjuvant CRT in patients with ESCC (Huang et al: Jpn J Clin Oncol. 2015;45:1023–8). However, a direct comparison of two CRT regimens in a prospective randomized clinical trial has not been performed in ESCC. We designed this clinical trial to test the hypothesis that paclitaxel-platinum is superior to PF as neoadjuvant CRT in patients with locally advanced ESCC. Methods: This single center open-label phase 2/3 study randomizes patients with histologically confirmed ESCC, T3/4aN0M0 or T1-3N1-3M0 (AJCC 7th edition), in 1:1 ratio, to receive TP (paclitaxel, 50 mg/m2/week; cisplatin 30 mg/m2/week; for 5 weeks) or PF (cisplatin 75 mg/m2, d1; 5-FU 1,000 mg/m2, d1-4; on week 1 and week 5)-neoadjuvant CRT (180 cGy/d, 5 days/week, for 5 weeks). Esophagectomy will be performed 6 to 10 weeks after completing CRT. All patients must be eligible to esophagectomy, with tumor length ≤8cm and tumor radial ≤5cm, with adequate organ functions, and have ECOG performance status of 0-2. In the phase 2 stage, 128 patients will be enrolled, assuming the pathologic complete response (pCR) rate of TP and PF as 45% and 25%, respectively, with a power of 80% and one-sided 10% significance level. If the primary endpoint of pCR is met, additional 120 patients will be enrolled for the phase III stage with overall survival as the primary endpoint, assuming the hazard ratio of TP versus PF as 0.65 with a power of 80% and a 5% significance level. The trial started patient enrollment in May, 2017. As of Jan of 2020, 52 of planned 128 patients for phase II part have been enrolled. Clinical trial information: NCT03623737 .

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