Phase II study of docetaxel in combination with oxaliplatin in patients with metastatic or locally advanced esophagogastric cancer previously untreated with chemotherapy for advanced disease. Results of the CECOG-Study ESGAS.1.2.001

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4527-4527 ◽  
Author(s):  
M. Hejna ◽  
J. Zacherl ◽  
A. Ba-Ssalamah ◽  
A. Püspök ◽  
U. Pluschnig ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Locally Advanced ◽  
Primary Objective ◽  
Hematologic Toxicity ◽  
Time To Progression ◽  
Who Grade ◽  
Esophagogastric Cancer ◽  
Gastroesophageal Adenocarcinoma ◽  
Grade 3

4527 Background: A phase II trial was performed to determine the antitumor efficacy and tolerance of combined docetaxel and oxaliplatin in previously untreated, advanced patients with gastroesophageal adenocarcinoma. Methods: Thirty-six patients with histologically confirmed advanced gastroesophageal adenocarcinoma were entered in this trial. Treatment consisted of 3-weekly courses of docetaxel 80 mg/m2 and oxaliplatin 100 mg/m2 both given on day 1. A 5-day course of human granulocyte colony stimulating factor (G-CSF) 5 μg/kg/day was given subcutaneously to prevent neutropenia; in addition, if haemoglobin was <12.0 mg/dl, erythropoietin 10,000 IU was administered subcutaneously 3 times per week. Primary objective was to evaluate the time to progression. Results: The confirmed overall response rate was 36%, including 3 complete responses (8.3%) and 10 partial responses (27.7%). Fifteen patients (41.7%) had stable disease and 8 (22.3%) progressed while on treatment. The median time to response was 2.5 months, the median time to progression was 5.3 (1- 33+) months and the median overall survival time was 9.8 (2.5–35+) months with 8 (22%) patients currently alive. Hematologic toxicity was common, though WHO grade 3/4 neutropenia occurred only in 6 (17%) patients and anaemia also in 6 (17%) patients, respectively. Nonhematologic adverse reactions were usually mild to moderate; grade 3 toxicities included emesis, diarrhoea and mucositis each in 1 patient (3%). Conclusion: Our data suggest that the combination of docetaxel and oxaliplatin with G-CSF and erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal adenocarcinoma. No significant financial relationships to disclose.

Preliminary Results of a Phase II Trial of Panobinostat (LBH589) In Refractory Myelodysplastic Syndromes (MDS) Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4015-4015 ◽  
Author(s):  
Ian W. Flinn ◽  
Evan Lang ◽  
Eric Raefsky ◽  
Ralph Boccia ◽  
Inés M. Macias-Pérez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Failure ◽  
Clonal Evolution ◽  
Primary Objective ◽  
Hematologic Toxicity ◽  
Combination Regimen ◽  
White Males ◽  
Duration Of Response ◽  
Grade 3 ◽  
Ecog Ps

Abstract Abstract 4015 Background: MDS represents a heterogeneous group of clonal myeloid stem cell disorders with a propensity for clonal evolution with resultant progressive bone marrow failure and transformation to acute myeloid leukemia. These disorders are incurable with conventional therapy and are usually treated with hypomethylating agents and supportive care. Panobinostat (PAN, LBH589) is a pan deacetylase (DAC) inhibitor that targets a variety of tumor types, including acute and chronic leukemia, by inhibiting differentiation and inducing apoptosis. Method: This single-arm multicenter Phase II study was designed with the primary objective of assessing the overall response rate (CR, marrow CR + PR) of PAN in patients (pts) with relapsed or refractory MDS. Secondary endpoints include time-to-progression, hematologic improvement, duration of response, time-to-treatment failure, and survival. Eligible pts had histologically documented MDS, previous failure on hypomethylating (azacitidine or decitabine) therapy, no prior treatment with DAC inhibitors, no active CNS disease, and adequate organ function. Pts with up to and including 30% blasts were eligible to enroll; pts with 5q- abnormalities must have failed lenalidomide. PAN (30mg PO) was administered three times a week on Monday, Wednesday and Friday. Pts were treated for the first 21 days of a 28 day cycle. If no grade 3/4 toxicity occurred in the first 2 cycles, dose escalation (40mg PO M/W/F) would proceed. Results: The original protocol for this trial specified a dose of 20mg PAN M/W/F, which was generally well-tolerated. Accumulating data from other studies suggested that higher doses of PAN were more efficacious without a significant increase in toxicity. The dose of PAN was thus increased to 30mg M/W/F in the amended protocol. To date, 16 pts have been enrolled at 30mg; this analysis is based on 10 pts enrolled from October 2008 through December 2009; all pts in this group are ECOG PS 0 white males (median age 77years [range 62–86]). The most common non hematologic adverse events were: anorexia (5 G1/2) fatigue (8 G1/2 and 1 G3) and nausea (3 G1/2). Hematologic toxicity was assessed on an ongoing basis: 5 pts experienced G3/4 anemia; 8 G3/4 thrombocytopenia; 6 G3/4 leukopenia, and 7 G3/4 neutropenia. Response was assessed after 2 cycles. Seven of 10 pts had stable disease; 2 pts had progressive disease; 1 pt was unevaluable due to coming off study prior to evaluation. 2 of the 10pts were escalated to the 40mg dose level. There were 6 SAEs (among 3 pts) for: G3 febrile neutropenia (2), G3 neutropenia (1), G3 pain (1), G4 pneumonia (1) and G4 thrombocytopenia (1). Nine pts are currently alive with a median follow-up of 69 weeks (range 28–90). Conclusions: Collectively, these data suggest that PAN is generally well-tolerated in pts with refractory MDS. Continued investigation of this novel agent is warranted, and future studies should evaluate its safety and efficacy when used as part of a combination regimen. Disclosures: Flinn: Novartis: Research Funding.

ICORG 06-41: A phase II trial of single-agent sorafenib in the treatment of platinum-pretreated relapsed gastroesophageal adenocarcinoma (GECa).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 88-88 ◽  
Author(s):  
Louise Catherine Connell ◽  
Seamus O'Reilly ◽  
Glenn Webb ◽  
Brian Moulton ◽  
Imelda Parker ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Locally Advanced ◽  
Safety Data ◽  
Primary Objective ◽  
Open Label ◽  
Oncology Research ◽  
Translational Studies ◽  
Gastroesophageal Adenocarcinoma

88 Background: Over 1 million individuals worldwide annually are diagnosed with GECa. The majority of patients(pts) present with inoperable locally advanced or metastatic disease(dx). Even with resectable dx 5 year survival is low at ~40% with current best treatment (tx). Following initial platinum based therapy there is no established standard 2nd line tx. Besides HER2-directed therapy there has been little progress with targeted biologic agents. ICORG, the all-Ireland Cooperative Oncology Research Group investigated the utility of the tyrosine kinase inhibitor sorafenib in a multicentre trial. Methods: A prospective Phase II, nonrandomised, open label, one arm study of single agent sorafenib in the tx of platinum pre-treated relapsed GECa was conducted. Primary objective was dx control rate (DCR) post 4 months of tx. Secondary endpoints were OS, PFS, TTP, ORR, tolerability/toxicity and biomarkers of tx response/resistance. The protocol allowed for an interim analysis to be performed if clinically indicated. A sample size of 54 pts was identified using the single stage Fleming design approach to test whether the proportion responding, P, is ≤ 0.35 or ≥ 0.50. Pts received Sorafenib 400mg bid p.o. continuously q28days until dx progression or intolerable toxicity. Response by RECIST was evaluated by CT q8weeks. For pts with sufficient tumour samples translational studies were done. Results: An interim review performed in Nov 2012 (35 months post study opening) indicated that 33/41 evaluable pts recruited to date had progressed before completing 4 months of tx. Therefore, the number of evaluable pts with dx control could not reach the pre-specified figure of 22, & the hypothesis P >= 0.50 was rejected. Fifteen pts had just 1 cycle of tx, 5 of whom completed ≤ 2 weeks. A further 14 pts had 2 cycles. Median survival time to progression was 56 days (95% CI 53 – 59 days).Median OS was 120 days (95% CI 91 – 149 days). Safety data analyses and translational studies are ongoing and will be available for presentation at the meeting. Conclusions: Sorafenib as monotherapy is inactive in platinum pretreated pts with relapsed GECa. A significant unmet clinical need for novel effective therapies remains. Clinical trial information: 2008-005062-31.

Efficacy and safety of patupilone in non-small cell lung cancer (NSCLC): A phase I/II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7104-7104 ◽  
Author(s):  
J. M. Sánchez ◽  
A. Mellemgaard ◽  
M. Perry ◽  
P. Zatloukal ◽  
J. Hamm ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Brain Metastases ◽  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Primary Objective ◽  
Prior Treatment ◽  
Wide Range ◽  
Grade 3

7104 Background: Based on its activity in a wide range of tumors including those that are taxane resistant, the novel microtubule stabilizer patupilone (EPO906; epothilone B) has the potential to treat NSCLC. Fifty patients were enrolled in phase I to evaluate safety, efficacy, and optimal dose. The phase II part of this study is investigating the antitumor activity of patupilone in 53 patients with stage IIIB/IV NSCLC. Methods: Patients with histologically or cytologically confirmed unresectable, locally advanced, or metastatic NSCLC documented before 1st-line therapy without symptomatic or uncontrolled brain metastases received patupilone at a starting dose of 10.0 mg/m2 q3wk by 20-minute IV infusion. Additional inclusion criteria: age ≥18 years; WHO performance status 0–1; prior treatment with a platinum-containing regimen. Primary objective of the phase II, single-arm, 2-stage, multicenter trial: to determine activity of patupilone q3wk (overall response using modified RECIST) in NSCLC. An additional cohort with recurrent brain metastases from NSCLC is being accrued to evaluate safety, pharmacokinetics, and activity. Results: In phase I, all patients received prior treatment with platinum therapy; 28% had received taxanes and 78% nontaxanes. Patupilone dose was escalated from 6.5 to 13.0 mg/m2 q3wk. Dose-limiting toxicities occurred in 4 patients: 1 with grade 3 asthenia and 3 with grade 3 diarrhea at various dose levels. The most frequent adverse events (AEs) were diarrhea (66%), nausea (40%), vomiting (34%), paraesthesia (32%), abdominal pain (30%), and fatigue (30%). The most frequent grade 3 AE was diarrhea (14%); a grade 4 AE (asthenia) occurred in 1 patient. Overall phase I response: 5 PR, 16 SD, and 26 PD. Based on risk-benefit analyses, 10.0 mg/m2 q3wk was recommended as the phase II dose. Phase II is ongoing: 25 of 53 patients (15 men and 6 women with NSCLC; 2 men and 2 women with brain metastases) have been enrolled. Conclusions: In phase I, patupilone q3wk was safe and well tolerated, with antitumor activity in patients with advanced pretreated NSCLC. Data from phase II will be available at time of presentation. [Table: see text]

Phase II Multi-Institutional Randomized Trial of Docetaxel Plus Cisplatin With or Without Fluorouracil in Patients With Untreated, Advanced Gastric, or Gastroesophageal Adenocarcinoma

2005 ◽  
Vol 23 (24) ◽  
pp. 5660-5667 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Miguel B. Fodor ◽  
Sergei A. Tjulandin ◽  
Vladimir M. Moiseyenko ◽  
Yee Chao ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Randomized Study ◽  
Data Monitoring Committee ◽  
Experimental Treatment ◽  
Phase Iii ◽  
Time To Progression ◽  
Gastroesophageal Adenocarcinoma ◽  
Grade 3

Purpose The purpose of this study was to define the contribution of docetaxel to combination chemotherapy in the outcome of patients with advanced gastric or gastroesophageal adenocarcinoma. We compared the overall response rate (ORR) and safety of docetaxel plus cisplatin (DC) with DC plus fluorouracil (DCF) to select either DC or DCF as the experimental treatment in the ensuing phase III part of trial V-325. Patients and Methods In this phase II randomized study, untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received either DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2/d as continuous infusion on days 1 to 5) or DC (docetaxel 85 mg/m2 and cisplatin 75 mg/m2 on day 1) every 3 weeks. An independent data monitoring committee (IDMC) was to select one of the two regimens based primarily on ORR and safety profile. Results Of 158 randomly assigned patients, 155 (DCF, n = 79; DC, n = 76) received treatment. The confirmed ORR was 43% for DCF (n = 79) and 26% for DC (n = 76). Median time to progression was 5.9 months for DCF and 5.0 months for DC. Median overall survival time was 9.6 months for DCF and 10.5 months for DC. The most frequent grade 3 and 4 events per patient included neutropenia (DCF = 86%; DC = 87%) and GI (DCF = 56%; DC = 30%). Conclusion Both regimens were active, but DCF produced a higher confirmed ORR than DC. Toxicity profiles of DCF were considered manageable. The IDMC chose DCF for the phase III part of V-325, which compares DCF with cisplatin plus fluorouracil.

A randomized, phase II trial comparing sequential paclitaxel/cisplatin/gemcitabine/vinorelbine/ (PCGV) with cisplatin/gemcitabine/vinorelbine/ (CGV) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17008-17008
Author(s):  
J. De Castro ◽  
C. Belda-Iniesta ◽  
E. Casado Saenz ◽  
J. Feliu ◽  
M. Sereno ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Rank Test ◽  
Time To Progression ◽  
Who Grade ◽  
Log Rank Test ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Nsclc Patients

17008 Background: New effective therapies are needed to improve the outcome of patients with advanced NSCLC. In this regard, new approaches such as cisplatin-based triplets have been explored with promising results but high toxicity. Furthermore, sequential chemotherapy schedules with taxanes followed by cisplatin-based regimens or viceversa could improve activity. A phase II study showed that sequential chemotherapy with weekly paclitaxel followed by CGV was highly active. Methods: A multicenter, randomized phase II trial of PCGV vs CGV in advanced NSCLC patients was conducted. Primary end-point: time to progression and survival. Eligible pts had unresectable, histologically confirmed NSCLC; no prior chemotherapy; PS 0–2; measurable disease. Pts received: Arm A (PCGV): P 150 mg /m2/week × 6, followed 2 weeks later by C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Arm B (CGV): C 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV), every 28 days for a maximum of six courses. Results: 106 Pts were included. Pts baseline characteristics (A/B: 52/54): male 82/79%; median age 60/59 (range 38–75 years); PS 0: 30/33%; 1 63/60%; 2: 7/7%; % squamous carcinoma:44/42%.WHO grade 3–4 toxicities for P were: neutropenia 18%; anemia 10%; thrombocytopenia 2%, peripheral neuropathy 18%. Grade 3–4 toxicities for CGV after P were: neutropenia 31%,nausea-vomiting 20%,thrombocytopenia 7%,anemia 5%,peripheral neuropathy 21%. WHO grade 3–4 toxicities for arm B were: neutropenia 35%,nausea-vomiting 19%, anemia 12%, thrombocytopenia 11% and peripheral neuropathy 15%. After therapy with arm A, 44% achieved a partial response, 15% had stabilization and 41% progressed. Arm B response rate were as follows: partial response 33%, stable disease 24% and progressive disease 43%. Median time to progression was (A/B) 7/6 months (log rank test, p 0.13) and median survival was (A/B): 11/10 months (log rank test, p 0.5). Conclusions: In spite of high response rate in TCGV arm, no survival benefit was detected in advanced NSCLC patients. No significant financial relationships to disclose.

Phase I/II study of PCI-27483, a coagulation factor VIIa (FVIIa) inhibitor in patients with advanced pancreatic cancer receiving treatment with gemcitabine.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 221-221 ◽  
Author(s):  
R. K. Ramanathan ◽  
V. Gressler ◽  
S. Shah ◽  
D. Loury ◽  
A. Hamdy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Coagulation Factor ◽  
Hematologic Toxicity ◽  
Venous Thromboembolic Events ◽  
Grade 3 ◽  
To Receive

221 Background: PCI-27483 is a selective inhibitor of FVIIa, a serine protease activated by interaction with tissue factor (TF). TF upregulation in tumor cells correlates with angiogenesis and a worsened prognosis. Hydrolysis of protease activated receptors by the TF:FVIIa complex induces up-regulation of IL-8 and VEGF. PCI-27483 inhibited the growth of human pancreatic tumors in animal models at a 2.5x to 3.0x change in prothrombin time. PK/INR relationships from a phase I study in healthy volunteers were used to select initial doses of PCI-27483 for the current study. Methods: Patients (pts) with locally advanced or metastatic pancreatic cancer, ECOG performance status 0-1, and normal coagulation were enrolled. All pts in phase I and II receive gemcitabine (G) as a 30-min IV infusion at a dose of 1000 mg/m2 on 3 out of every 4 wks. PCI-27483 is administered twice daily by SC injection. In phase I, doses of PCI-27483 were intra-patient escalated (0.8 to1.2 to1.5 mg/kg) over 4 to 8 wks. The targeted peak INR, measured 2 h postdose, was 3.0. In phase II, pts are being randomized to a control arm to receive G only or to a PCI-27483 arm to receive G plus PCI-27483. Phase I pts receiving 80% of planned doses during in first 6 wks were considered evaluable. Spiral CT scans are performed at 8-wk intervals. Study endpoints: adverse event profile, progression-free survival, venous thromboembolic events, and overall survival. Results: Phase I—8 pts enrolled, 5 pts evaluable. Highest dose of PCI- 27483 achieved was 0.8 mg/kg for 2 pts, 1.2 mg/kg for 3 pts and 1.5 mg/kg for 3 pts. Hematologic toxicity: grade 3 neutropenia (n= 1) or anemia (n = 2). Other grade 3 toxicities: elevated INR (n = 4) or elevated aPTT (n = 1). Dose-level-specific mean 2-h INR values were 2.2 at 0.8 mg/kg (CV=9%; n=7), 3.2 at 1.2 mg/kg (CV=33%; n=6) and 2.9 at 1.5 mg/kg (CV=16%; n=3). No VTEs occurred. Radiologic evaluations of 5 evaluable pts: 4 SD at 16 wks (1st pt SD for >40 wks; 5th pt SD at 8 wks, 16-wk scan pending). Conclusions: PCI-27483 is well tolerated at doses up to 1.5 mg/kg bid with G 1,000 mg/m2. Sustained SDs occurred and INRs were generally within the expected range. The randomized phase II study is ongoing at a dose of 1.2 mg/kg bid. [Table: see text]

EXIBIT: An international multicenter phase II trial of gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4135-4135 ◽  
Author(s):  
T. André ◽  
J. M. Reyes-Vidal ◽  
L. Fartoux ◽  
P. Ross ◽  
M. Leslie ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Bile Ducts ◽  
Locally Advanced ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Extrahepatic Bile Ducts ◽  
Grade 3 ◽  
Ecog Ps

4135 Background: Biliary tract carcinomas (BTC) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) showed promising activity in a French Phase II study (4 centers) in advanced BTC (André. Ann Oncol 2004;15:1339–1343). The objective of this study is to further evaluate the efficacy and safety of GEMOX as first-line therapy in patients (pts) with advanced BTC. Methods: Eligible pts were >18 years of age with histologically proven and measurable, locally advanced or metastatic BTC, had an ECOG PS ≤ 2, adequate renal and hematologic functions, bilirubin < 2.5 × upper limit of normal, and no prior malignancy or brain metastases. Gemcitabine 1000 mg/m2 (Day 1) and oxaliplatin 100 mg/m2 (Day 2) were administered every 2 weeks. The primary objective was response rate (RR) by RECIST (one dimension); secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Here we report an interim analysis of OS and safety. Results: A total of 70 pts were enrolled between April 2003 and April 2005. The median age was 62 years (range 30–83), 40.0% of pts were male, 94.3% had ECOG PS 0–1. Tumor sites were intrahepatic bile ducts (37.1%), gallbladder (31.4%), extrahepatic bile ducts (12.9%), ampulla of Vater (1.4%), intra/extrahepatic bile ducts (1.4%), missing data (15.7%); 98.6% of pts had no prior radiotherapy and 50% had no prior surgery for BTC. Median OS is 8.25 months (68% of pts are dead and 32% have censored data). Sixty-seven pts were evaluable for safety. Grade 3/4 (NCI-CTC v. 2) hematologic toxicities (% of pts) included thrombocytopenia 10.4%, anemia 9.0%, and neutropenia 9.0%. One pt had febrile neutropenia. Grade 3/4 nonhematologic toxicities included pain 10.4%, ALT elevation 9.0%, fatigue 9.0%, infection 10.4%, vomiting 9.0%, sensory neuropathy 4.5%, nausea 4.5%, and diarrhea 3.0%. One patient died during treatment (cause unknown). Conclusions: GEMOX has acceptable toxicity in pts with BTC. Updated efficacy data (RR, PFS, and OS for the entire population and also by tumor sites) will be presented at the meeting. [Table: see text]

Epirubicin, Oxaliplatin, and Capecitabine With or Without Panitumumab for Advanced Esophagogastric Cancer: Dose-Finding Study for the Prospective Multicenter, Randomized, Phase II/III REAL-3 Trial

2010 ◽  
Vol 28 (25) ◽  
pp. 3945-3950 ◽  
Author(s):  
Alicia F.C. Okines ◽  
Sue E. Ashley ◽  
David Cunningham ◽  
Jacqueline Oates ◽  
Andrea Turner ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Undifferentiated Carcinoma ◽  
Dose Finding ◽  
Original Design ◽  
Esophagogastric Cancer ◽  
Finding Study ◽  
Grade 3

Purpose Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer. Panitumumab (P) is a fully human, immunoglobulin G2 monoclonal antibody targeting epidermal growth factor receptor. Randomized Trial of EOC ± Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL-3) will evaluate whether the addition of P to EOC improves survival in patients with advanced esophagogastric adenocarcinoma and undifferentiated carcinoma. Patients and Methods The original design of REAL-3 added P 9 mg/kg to the standard dose of EOC (dose level [DL] + 1). Due to toxicity, a dose de-escalation was made to EOC + P DL − 1 (epirubicin 50 mg/m2, oxaliplatin130 mg/m2, capecitabine 1,000 mg/m2/d + P 9 mg/kg every 3 weeks). After additional toxicity was observed, the study was amended to include two additional EOC + P dose levels. Using a 3 + 3 design, dose-limiting toxicities (DLTs) were assessed weekly during cycle 1. Patients were randomly assigned 1:1 to EOC ± P. Results Between July 2008 and October 2009, 29 patients were randomly selected for standard-dose EOC (n = 13) or EOC + P (n = 16). Five patients were treated at DL + 1, with grade 3 diarrhea in four of five patients by cycle 4. At DL − 1, one patient had grade 3 diarrhea and grade 5 infection. Three patients were treated at DL − 3, and then six were treated at DL − 2, without DLTs. Conclusion The recommended dose for EOC + P is epirubicin 50 mg/m2, oxaliplatin 100 mg/m2, capecitabine 1,000 mg/m2/d, and P 9 mg/kg every 3 weeks. This dose has been selected for the ongoing phase II/III REAL-3 study.

Phase II trial of preoperative bevacizumab (Bev), irinotecan (I), cisplatin (C), and radiation (RT) in esophageal adenocarcinoma: Preliminary safety analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4573-4573
Author(s):  
D. Ilson ◽  
M. Bains ◽  
N. Rizk ◽  
V. Rusch ◽  
R. Flores ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Surgical Complication ◽  
Wound Complications ◽  
Hematologic Toxicity ◽  
Esophagogastric Cancer ◽  
Toxicity Analysis ◽  
Grade 3 ◽  
C 30

4573 Background: Preo chemoRT with weekly I/C and 5040 cGy followed by surgery is well tolerated [JCO 24: Abstract 4032; 2006]. ECOG trial E1201recently reported a median survival of 34 months with this preop regimen [JCO 26: Abstract 4532; 2008]. Bev + chemo improves response rate (RR) and time to progression (TTP) when added to weekly I/C in advanced esophagogastric cancer but does not increase chemo toxicity [JCO 24: 5201; 2006]. We are now combining in a Phase II trial Bev/I/C with concurrent radiotherapy (RT) in esophageal adenocarcinoma (EA) with the primary endpoint of safety. Methods: Patients (pts) with resectable Siewert's I or II EA were staged by EUS, PET, and CT. Induction chemo consisted of I-50–65 mg/m2 and C-30 mg/m2 weeks 1,2,4,5, Bev-7.5 mg/kg weeks 1 and 4; and, during RT (180 cGy daily to 5040 cGy), I/C was given weeks 7,8,10,11 and Bev weeks 7,10. Esophagectomy was 6–8 weeks after RT. A planned toxicity analysis was made in 10–15 pts completing chemoRT, and in 10 pts undergoing surgery: toxicity was acceptable if grade 3 / 4 hematologic toxicity remained < 72% and non hematologic toxicity < 40% during combined chemoRT (based on our prior phase II trial of I/C/RT [JCO 24: Abstract 4032; 2006]); and if pts undergoing surgery had no surgical complication related to Bev. Results: 18 pts have been enrolled, 12 male: 6 female; 7 Siewert I: 11 Siewert II; T3N1 12: T3N0 5: T2N0 1. 14 are evaluable for toxicity, 2 are too early, one progressed prior to RT, and one was taken off due to a CVA from a patent foramen ovale. Grade 3/4 neutropenia occurred in 4 pts (29%). Grade 3/4 non heme toxicity occurred in 5 pts (36%), including esophagitis 2 pts (14%), neutropenic fever 1 pt (7%), and pulmonary embolism 1 pt (7%). No grade 3 / 4 hypertension was seen, and 3 pts (21%) developed grade 1 proteinuria. Ten pts underwent surgery, and there were no unexpected surgical or wound complications; there were 2 anastomotic leaks. Pathologic responses: 1 pathologic CR and 1 T0N1. Conclusions: In a preliminary analysis of pts treated with Bev + preop chemoRT in EA, there was no increase in hematologic/non hematologic toxicity or Bev related surgical complications. Accrual will continue to 33 patients. Supported by Genentech. [Table: see text]

N0321: A phase II study of bortezomib, paclitaxel, carboplatin (CBCDA), and radiotherapy (RT) for locally advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7073-7073
Author(s):  
Steven E. Schild ◽  
Nathan R. Foster ◽  
Julian R. Molina ◽  
Grace K. Dy ◽  
Kendrith M. Rowland ◽  
...  
Keyword(s):  
Survival Rate ◽  
Adverse Events ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Hematologic Toxicity ◽  
Tumor Killing ◽  
Grade 3 ◽  
Ecog Ps

7073 Background: In preclinical studies, combinations of bortezomib and RT result in synergistic tumor killing (Cancer Chemother Pharmacol. 2007;59:207-15). Our group reported the results from the phase I portion of this study previously (J Clin Oncol. 200;28 (suppl; abstr 7085)). Based on these data, we undertook a phase II study of bortezomib in combination with paclitaxel/CBCDA and RT. Methods: Based on results from our previously reported phase I trial, systemic therapy included bortezomib (1.2 mg/m² IV days 1,4,8,11), paclitaxel (175 mg/m² IV day 2), and carboplatin (CBCDA; AUC=6 day 2) given every 3 weeks for 2 cycles. Thoracic radiotherapy (RT) included 60Gy/30 daily fractions starting day 1. The primary endpoint was the 12-month survival rate. If 41 or more of these 60 patients (68%) were alive at least 12 months after study entry, the trial would be deemed as positive and further study would be warranted. Results: 27 pts were enrolled to the phase II portion: M/F=17/10; stage IIIA/IIIB=13/14; ECOG PS 0/1=9/18; and median age: 58 (range 43-79). 18 pts (67%) completed therapy per protocol. At a planned interim analysis, 23 of 26 evaluable patients (88.5%, 95% CI: 70-98%) survived for at least 6 months, which exceeded the boundary of 21 or more needed to continue to full accrual. This trial could have continued per protocol, but was closed early due to slow accrual. With a median follow-up of 15.0 months in the 17 patients still alive, the 12-month survival rate was 71% (95% CI: 49 – 85). The median OS was 19 months (95% CI: 11 – no upper). Grade 3 or higher adverse events (regardless of attribution) were reported in 22 (82%) patients. Grade 4/5 adverse events were reported in 15 (56%) patients. There was one grade 5 event (pneumonitis). The most common (5 or more patients) grade 3/4 adverse events were fatigue (22%), leukopenia (63%), neutropenia (67%), and thrombocytopenia (44%). Conclusions: The addition of bortezomib resulted in high levels of severe hematologic toxicity, but also demonstrated evidence of activity with a 12-month survival rate of 71% and a median OS of 19 months. Further testing of this regimen in a larger study appears warranted.

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