A phase II, open-label pilot study evaluating the safety and activity of nal-IRI in combination with 5-FU and oxaliplatin in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS476-TPS476
Author(s):  
Hiral D. Parekh ◽  
David L. DeRemer ◽  
Kathryn Hitchcock ◽  
Susan P. McGorray ◽  
Allison Allegra ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Care Delivery ◽  
Neoadjuvant Treatment ◽  
Eastern Cooperative Oncology Group ◽  
R0 Resection ◽  
Preoperative Treatment ◽  
Open Label ◽  
Borderline Resectable ◽  
Patient Reported

TPS476 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a very tolerable safety profile in refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and demonstrate safe and effective delivery in the neoadjuvant setting. Methods: This phase II, open-label, single-arm study targets patients with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥ 18 years, measurable disease by RECIST v1.1, adequate cardiac, renal, hepatic function, and Eastern Cooperative Oncology Group performance status of 0 to 1. Patients receive FOLFNal-IRINOX regimen as per table every two weeks for four months followed by disease reassessment. Patients who remain surgical candidates will undergo surgical resection within four to eight weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable patients to demonstrate a reduction in historical 30 day postoperative complication rate. FOLFNal-IRINOX regimen. Clinical trial information: NCT03483038. [Table: see text]

A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS446-TPS446
Author(s):  
Brian Hemendra Ramnaraign ◽  
Steven J. Hughes ◽  
Kathryn Hitchcock ◽  
Ji-Hyun Lee ◽  
Sherise C. Rogers ◽  
...  
Keyword(s):  
Phase Ii ◽  
Care Delivery ◽  
Performance Status ◽  
Neoadjuvant Treatment ◽  
Tumor Board ◽  
R0 Resection ◽  
Preoperative Treatment ◽  
Open Label ◽  
Patient Reported ◽  
Liposomal Irinotecan

TPS446 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase II, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NALIRIFOX regimen as per the table below every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30 day postoperative complication rate. Clinical trial information: NCT03483038. [Table: see text]

A phase II, open-label pilot study evaluating the safety and activity of Nal-IRI in combination with 5-FU and oxaliplatin in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study) (NCT03483038).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS790-TPS790
Author(s):  
Hiral D. Parekh ◽  
Jessica L. Cioffi ◽  
Kathryn Hitchcock ◽  
Ji-Hyun Lee ◽  
Z. Hugh Fan ◽  
...  
Keyword(s):  
Care Delivery ◽  
Performance Status ◽  
Neoadjuvant Treatment ◽  
Tumor Board ◽  
R0 Resection ◽  
Preoperative Treatment ◽  
Open Label ◽  
Borderline Resectable ◽  
Standard Regimen ◽  
Patient Reported

TPS790 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board, adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive FOLFNal-IRINOX regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30 day postoperative complication rate. Clinical trial information: NCT03483038 . [Table: see text]

A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI study) (NCT03483038).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4170-TPS4170
Author(s):  
Sherise C. Rogers ◽  
Brian Hemendra Ramnaraign ◽  
Kathryn Hitchcock ◽  
Steven J. Hughes ◽  
Ji-Hyun Lee ◽  
...  
Keyword(s):  
Care Delivery ◽  
Performance Status ◽  
Neoadjuvant Treatment ◽  
Tumor Board ◽  
R0 Resection ◽  
Preoperative Treatment ◽  
Open Label ◽  
Standard Regimen ◽  
Patient Reported ◽  
Liposomal Irinotecan

TPS4170 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NALIRIFOX regimen as per the table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30 day postoperative complication rate. NCT03483038. NALIRIFOX regimen components given intravenously (IV) every 14 days. Clinical trial information: NCT03483038. [Table: see text]

scholarly journals Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation

2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Open Label ◽  
Free Survival ◽  
Palb2 Mutation

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

A multicenter phase II study of thalidomide in combination with interleukin-2 (IL-2) in patients with previously untreated metastatic renal cell carcinoma (MRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14636-14636 ◽  
Author(s):  
D. Farray ◽  
J. I. Clark ◽  
T. Kuzel ◽  
J. P. Dutcher
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Group Performance ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Interleukin 2 ◽  
Open Label ◽  
Anti Tumor Activity

14636 Background: Thalidomide, a drug with immune modulating and anti-angiogenic properties has shown activity in relapsed/refractory MRCC; furthermore, early phase I data of oral thalidomide with subcutaneous low-dose IL-2 showed the combination to be safe. The potential anti-tumor activity of this combination formed the basis of this study. Methods: The aim of this multi-center, open label, phase II study was to determine the efficacy and safety of thalidomide and IL-2 given in combination. Patients (pts) with untreated clear cell MRCC with measurable disease and previous nephrectomy were eligible. Two 6-week cycles of thalidomide and IL-2 were planned. Each cycle consisted of thalidomide started at 200 mg orally daily and titrated to 400 mg daily on the 4th day for 6 weeks; IL-2 was started one week post initiation of thalidomide at a dose of 7mIU/m2 subcutaneously days 1–5 for 4 weeks, followed by 2 weeks off therapy. Therapy was to be continued until progression, if there was at least stable disease (SD). Planned accrual was 53 patients. Results: 11 pts were enrolled. The trial was terminated early due to lack of responses. Median age was 57 years (51–66). All pts had an Eastern Cooperative Oncology Group performance status of 2 or better. The only grade 3 toxicities were fatigue (3 pts), neuropathy (1 pt), anorexia (1 pt), dyspnea (1 pt), edema (1 pt); these required dose reductions as per protocol. There were no objective responses: 3 pts had SD, 8 pts had progressive disease (PD). The 3 pts with SD completed 4, 4, and 6 cycles of therapy respectively; of the 8 pts with PD, 3 completed two cycles, and 5 completed one cycle of therapy. Conclusions: The combination of thalidomide and low-dose IL-2 was well tolerated, but in this trial did not show anti-tumor activity in patients with clear cell MRCC. We thank Celgene for support of this trial. No significant financial relationships to disclose.

scholarly journals Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000698
Author(s):  
Jean-Baptiste Bachet ◽  
Lucjan Wyrwicz ◽  
Timothy Price ◽  
Chiara Cremolini ◽  
Jean-Marc Phelip ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Open Label ◽  
Patient Reported ◽  
Registration Number ◽  
Grade 3

BackgroundIn RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.MethodsIn this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).Results793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03–14.72). There was no clinically relevant change from baseline in QoL.ConclusionsPRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.Trial registration numberNCT03306394.

Neoadjuvant chemo-immunotherapy for the treatment of stage IIIA resectable non-small-cell lung cancer (NSCLC): A phase II multicenter exploratory study—Final data of patients who underwent surgical assessment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8509-8509 ◽  
Author(s):  
Mariano Provencio ◽  
Ernest Nadal ◽  
Amelia Insa ◽  
Rosario Garcia-Campelo ◽  
Joaquín Casal Rubio ◽  
...  
Keyword(s):  
Phase Ii ◽  
Neoadjuvant Treatment ◽  
Progression Free Survival ◽  
Pathologic Response ◽  
R0 Resection ◽  
Complete Pathologic Response ◽  
Stage Iiia ◽  
Open Label ◽  
Multicentric Study ◽  
Final Data

8509 Background: Patients with stage IIIA (N2 or T4N0) are potentially curable but median overall survival is only around 15 months and complete pathologic response with conventional chemotherapy (CT) is no more than 9%. Methods: A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC adult patients with CT plus IO as a neoadjuvant treatment: three cycles of Nivolumab (NV) 360mg IV Q3W + paclitaxel 200mg/m2 + carboplatin AUC 6 IV Q3W followed by adjuvant NV treatment for 1 year. After complete neoadjuvant therapy, tumor assessment is performed prior to surgery. Surgery is performed in the 3rd or 4th week after day 21 of the third cycle of neoadjuvant treatment. The study aims to recruit 46 pts. The primary endpoint is Progression-Free Survival (PFS) at 24 months. Efficacy is explored using objective pathologic response criteria. We present final data on all patients included in this study that underwent surgical assessment. Results: At the time of submission, 46 pts had been included and 41 had undergone surgery. CT-IO was well-tolerated and surgery was not delayed in any patient. None of the pts withdrew from the study preoperatively due to progression or toxicity. 41 surgeries had been performed and all tumors were deemed resectable, with R0 resection in all cases. 34 pts (83%) achieved major pathologic response (MPR) (CI 95% 71-95%), and 24 (71%) of them had a complete pathologic response (CPR) (CI 95% 54-87%). Downstaging was seen in 90% (CI 95% 81-100%) of cases. By RECIST, 29 pts (71%) (CI 95% 56-85%) had partial response and 3 (7%) (CI 95% 0-16%) complete response. Conclusions: This is the first multicentric study to CT-IO in the neoadjuvant setting in stage IIIA. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a high complete pathologic response rate that has never been seen previously and unsuspected by RECIST criteria. Preliminary correlative analyses in blood samples are included in a separate abstract. EudraCT Number: 2016-003732-20. Clinical trial information: NCT 03081689.

A phase II trial of preoperative FOLFIRINOX followed by gemcitabine-based chemoradiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4638-4638
Author(s):  
Michael Wysota ◽  
Amanda Jirgal ◽  
Ana Acuna-Villaorduna ◽  
Shankar Viswanathan ◽  
Andreas Kaubisch ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Second Phase ◽  
Preoperative Treatment ◽  
Resection Rate ◽  
Borderline Resectable ◽  
Study Results

4638 Background: Preoperative (preop) therapy is widely accepted as the standard of care for patients (pt) with BR PDAC with limited evidence for a specific regimen. This study aimed to assess the efficacy of FOLFIRINOX (FOL) chemotherapy followed by gemcitabine-based chemo-radiotherapy (RT) as preop therapy in pt with BR-PDAC. Methods: This single arm Simon two stage phase II trial in pt with BR PDAC was conducted in two phases. The first phase included 4 cycles of FOL, and the second included weekly gemcitabine (1000 mg/m2) for 6 cycles with concomitant intensity-modulated RT (50.4 Gy in 28 fractions)(Gem/RT).The primary aim was to compare R0 resection rate (H0: ≤40% vs Ha≥60%) using one-sample one-sided Z test. Secondary outcomes, including overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier method. Results: Of 22 enrolled pt, 18 (81.8%) completed preoperative treatment. Median age at diagnosis was 63.4 years and 12 (54.5%) were female. There were 10 (45.5%) Hispanics, 4 (18.2%) non-Hispanic black, and 8 (36.4%) non-Hispanic white. Tumor location was predominantly head/neck (21, 95.5%), 15 (68.1%) had T2/3, and 9 (40.9%) had N2 (clinical) disease. Fourteen (64.6%) pt, had venous involvement, 5 (22.7%) had arterial, and 3 (13.6%), both. In the first phase, 20 (90.9%) completed 4 cycles of FOL, 6 (27.3%) required dose-reduction and dose was delayed in 12 (54.5%). Stable disease (SD) was achieved in 10 (52.6%), partial response (PR) in 8 (42.1%) and disease progression (PD) in 1 (5.3%) pt. Of 21 pt that entered the second phase, 18 (85.7%) completed 6 cycles of Gem/RT, 5 (26.3%) required dose-reduction and dose was delayed in 6 (31.6%). SD was achieved in 10 (55.6%), PR in 3 (16.7%) and PD in 5 (27.8%). All pt experienced at least one grade 1 adverse event (AE) and 12 (54.5%) at least one grade 3/4 AE, of which neutropenia was the most common-11 (50%). Of the 15 (68.1%) pt who underwent surgical resection, 12 (80%) achieved R0 margins and 5 (33.3%) required vascular reconstruction. The R0 rate among pt that received >1 cycle of FOLFIRINOX was 54.5%. Adjuvant chemotherapy was offered to 6/15 pt (40%). The PFS and OS will be reported. Conclusions: An R0 resection rate of 54.5% with this limited sample size is significant at the 10% level. Neoadjuvant FOLFIRINOX followed by concomitant Gem/RT was well-tolerated. The study will be amended to include adjuvant FOL in line with the PRODIGE intergroup adjuvant study results. Clinical trial information: NCT01897454 .

A phase II open-label study of cpi-613 in combination with modified (m)FOLFIRINOX in patients with locally advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4176-TPS4176
Author(s):  
David Lawrence Bajor ◽  
AMR MOHAMED ◽  
J. Eva Selfridge ◽  
Erin E. Anderson ◽  
Jeffrey Hardacre ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Open Label ◽  
Borderline Resectable ◽  
Nccn Guidelines

TPS4176 Background: For patients with locally advanced pancreatic cancer, neoadjuvant trials are the preferred strategy. The goals of neoadjuvant treatment are to diminish the size of the primary tumor to allow for safe surgical resection and to limit the chance of developing metastatic disease. mFOLFIRINOX is the gold-standard for treatment in the adjuvant setting and an acceptable regimen in the neoadjuvant setting with many ongoing neoadjuvant trials using it as a chemotherapeutic backbone. CPI-613 (devimistat) is a small-molecule inhibitor of pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase that has been studied in combination with mFOLFIRINOX in a phase I trial of patients with metastatic pancreas cancer and shown to be safe at the proposed phase II dose. Methods: This is a single-center, single-arm phase II trial for patients with locally advanced pancreatic cancer; defined as either borderline resectable or unresectable according to NCCN guidelines and interpreted by the primary investigator. Patients with metastatic disease are excluded. Patients will receive treatment with CPI-613 and mFOLFIRINOX per the table below. The primary endpoint is overall survival. Secondary endpoints are progression free survival and resection rate. At the time of submission this study has completed initial accrual with 37 patients enrolled. Clinical trial information: NCT03699319. [Table: see text]

Randomized, Double-Blind, Placebo-Controlled, Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non–Small-Cell Lung Cancer

2011 ◽  
Vol 29 (18) ◽  
pp. 2582-2589 ◽  
Author(s):  
David R. Spigel ◽  
Howard A. Burris ◽  
F. Anthony Greco ◽  
Dianna L. Shipley ◽  
Elke K. Friedman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Small Cell Lung

Purpose Sorafenib, an oral multikinase inhibitor, has shown preliminary activity in non–small-cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial. Patients and Methods Key eligibility criteria included the following: stage IIIB or IV NSCLC; one to two prior regimens; Eastern Cooperative Oncology Group performance status of 0 to 2; and measurable disease. Patients were randomly assigned 2:1 to sorafenib (400 mg orally twice a day) plus erlotinib (150 mg orally daily) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab. Treatment efficacy, measured by progression-free survival (PFS) and overall response rate (ORR), was compared. Treatment of 168 patients allowed detection of 40% improvement in the historical PFS of 2.2 months with single-agent erlotinib. Results One hundred sixty-eight patients enrolled from February 2008 to February 2009. Clinical characteristics of the two groups were similar. ORRs for sorafenib/erlotinib and placebo/erlotinib were 8% and 11%, respectively (P = .56); disease control rates were 54% and 38%, respectively (P = .056). Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib (hazard ratio, 0.86; 95% CI, 0.60 to 1.22; P = .196). Seventy-two patients consented to analyses of tumor epidermal growth factor receptor (EGFR). In 67 patients with EGFR wild-type (WT) tumors, median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib (P = .018); median overall survival (OS) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib (P = .019). An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization (FISH) EGFR-negative tumors (P = .064). Both regimens were tolerable, with modest toxicity increase with sorafenib. Conclusion Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH–negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.

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