SWOG 0941: A phase II study of sorafenib and erlotinib in patients (pts) with advanced gallbladder cancer or cholangiocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4113-4113 ◽  
Author(s):  
Anthony B. El-Khoueiry ◽  
Cathryn J Rankin ◽  
Syma Iqbal ◽  
Kenneth C. Micetich ◽  
Omar Kayaleh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gallbladder Cancer ◽  
Primary Endpoint ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Biology ◽  
Primary Objective ◽  
Prognostic Impact ◽  
Eligibility Criteria ◽  
Histologic Diagnosis

4113 Background: The treatment of pts with advanced biliary cancers represents a therapeutic challenge. The vascular endothelial growth factor and epidermal growth factor receptor pathways play an important role in biliary carcinogenesis, as evidenced by their up-regulation and prognostic impact. Methods: The primary objective was progression free survival (PFS) (improvement in PFS from 4 to 8 months); secondary endpoints included overall survival (OS), objective response rate, and toxicity. A two-stage design was used; if 13 or more eligible pts of the 25 initially accrued were alive without progression at 4 months, an additional 25 were to be accrued. Eligibility criteria included no prior treatment for advanced or metastatic disease, histologic diagnosis of gallbladder cancer or cholangiocarcinoma, presence of measurable disease, Zubrod performance status 0-1, AST/ALT ≤ 5 IULN, total bilirubin ≤1.5 IULN, adequate hematologic function. Pts were treated with sorafenib 400 mg PO BID and erlotinib 100 mg PO q daily continuously. Restaging scans were performed every 8 weeks. Results: 32 eligible pts were accrued. 30 pts were evaluable for response. 2 patients (7 %) had an unconfirmed partial response (95% CI:1%-23%), and 8 pts (27%) had stable disease. Median PFS was 2 months (95% CI: 2-3 months). 22/32 patients progressed or died within 4 months of registration. Median OS was 6 months (95% CI: 3 -7 months). The study failed to meet its primary endpoint to proceed to the second stage of accrual. There were 3 deaths on study, 1 of which was possibly related to treatment. 19 patients (59%) had grade 3 or 4 toxicities: AST/ALT (22%), bilirubin (16%), alkaline phosphatase (16%), hypertension (16%), diarrhea (9%), hepatic infection (6%). Conclusions: This multicenter study was the first to evaluate the combination of sorafenib and erlotinib in pts with advanced biliary cancers. Despite manageable toxicity, the study failed to meet its primary endpoint. Correlative studies on collected tissue and blood are ongoing; improved pt selection based on tumor biology and molecular markers is necessary for future evaluation of targeted therapies in this disease.

Randomized phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6015-6015
Author(s):  
Julie E. Bauman ◽  
Nabil F. Saba ◽  
Denise Roe ◽  
Jessica R. Bauman ◽  
John M. Kaczmar ◽  
...  
Keyword(s):  
Lower Bound ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Primary Objective ◽  
Phase Iii ◽  
Platinum Resistance ◽  
Eligibility Criteria ◽  
Immune Biomarkers ◽  
Hpv Status

6015 Background: Cetuximab (C), an anti-EGFR monoclonal antibody (mAb), is approved for advanced HNSCC but benefits a minority. Crosstalk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways is a known resistance mechanism. HGF is also immunosuppressive within the tumor microenvironment. A Phase I study confirmed the safety of C and ficlatuzumab (F), an IgG1 anti-HGF mAb, with preliminary efficacy and biomarker data suggesting that dual pathway inhibition may overcome tumor-intrinsic or immune cetuximab resistance. Methods: The primary objective of this phase II randomized, non-comparative trial was to evaluate the efficacy of F (20 mg/kg every 2 wks), with or without C (500 mg/m2 every 2 wks), in pan-refractory, advanced HNSCC. Eligibility criteria included recurrent/metastatic HNSCC, performance status (PS) 0-1, C resistance (defined as progression on or within 6 months of exposure), and resistance to or ineligibility for platinum and anti-PD1 mAb. Randomization was stratified by HPV status and center. The primary endpoint was median progression-free survival (mPFS). An arm was deemed worthy of further study if the lower bound of the 90% 1-sided confidence interval (CI) excluded the historical control of 2 months. Secondary objectives included overall response rate (ORR) in the overall and HPV-stratified populations. A Bayesian continuous monitoring rule for futility was applied. Results: 60 patients were randomized and 58 treated between Jan 2018 and Dec 2020 (27 to F; 33 to FC). Baseline characteristics were balanced across major prognostic variables including age, PS, HPV status, platinum resistance, and PD1 mAb exposure. Median time since prior cetuximab was 3.5 months (range 0-48 months). Grade ≥3 adverse events attributed to F included: pneumonitis (2); edema (3); diarrhea (1); LFT elevation (1); rash (2); electrolyte abnormality (2). The Table presents efficacy data. The F arm stopped for futility after 26 evaluable subjects accrued. The FC arm completed accrual and met the primary endpoint; 32 evaluable subjects had mPFS of 3.6 months (lower bound 90% 1-sided CI: 2.3 months) and ORR of 19% (6/32). All responses were in HPV- subjects, including 2 complete (CR) and 4 partial responses (PR) to the FC combination and 1 PR to F monotherapy. The mPFS and ORR for the HPV- population (n = 16) on FC were 3.8 months and 38% (6/16). Mechanistic signaling and immune biomarkers are under analysis. Conclusions: The well-tolerated FC combination met the primary PFS endpoint in pan-refractory, advanced HNSCC with notable activity in HPV- HNSCC, warranting phase III investigation. Clinical trial information: NCT03422536. [Table: see text]

Phase Ib study of talimogene laherparepvec (T-VEC) injection into liver metastases (LMs) in combination with intravenous (IV) atezolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or colorectal cancer (CRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS725-TPS725
Author(s):  
J. Randolph Hecht ◽  
Arlene Chan ◽  
Miguel Martin ◽  
Nicolas Mach ◽  
Sara A. Hurvitz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Intralesional Injection ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
The Usa

TPS725 Background: T-VEC is a genetically modified, oncolytic herpes simplex virus type 1 designed to selectively replicate within tumors and produce GM-CSF to enhance systemic antitumor immune responses. Atezolizumab is a monoclonal antibody checkpoint inhibitor (CPI) that targets PD-L1. The safety of intrahepatic administration of T-VEC has been demonstrated in a prior clinical trial (NCT02509507). A previous trial of T-VEC in combination with a CPI in advanced melanoma demonstrated improved responses compared to those with a CPI alone (Puzanov et al. JCO. 2016; 34:2619-26). We hypothesize that T-VEC combined with a CPI may also be effective in other tumor types. This phase 1b, multicenter study evaluates the safety of intrahepatic injection of T-VEC in combination with IV atezolizumab in pts with TNBC or CRC with LMs. Methods: The study will enroll up to 36 pts in two parallel cohorts (18 TNBC, 18 CRC) at sites in the USA, Europe, and Australia. The primary objective is to evaluate the incidence of dose-limiting toxicities (DLTs). Secondary objectives include objective response rate, lesion-level responses in injected and uninjected tumors, progression-free survival, and overall survival. Key eligibility criteria include age ≥ 18 years, confirmed diagnosis of TNBC or CRC with LMs, ECOG performance status 0/1, adequate organ function, disease progression during or after ≥ 1 prior standard-of-care systemic therapy for metastatic disease, and ≥ 1 measurable, injectable LM. T-VEC will be given by image-guided intralesional injection of up to 4 mL of 106 plaque forming units (PFU)/mL on day 1 and up to 4 mL of 108 PFU/mL every 21 days thereafter; atezolizumab 1,200 mg IV will be given on day 1 and every 21 days thereafter. The DLT-evaluation period is the first two cycles (1 cycle = 21 days). Interim safety analysis will occur after the first 4–6 pts have become DLT evaluable. Up to six cycles of T-VEC will be given with an additional 6 cycles allowed. After cycle three, nonhepatic lesions may be injected, subject to protocol-defined criteria. The study opened for enrollment in January 2018. (NCT03256344) Clinical trial information: NCT03256344.

Efficacy and safety of perioperative chemotherapy with 5FU-cisplatine-cetuximab in gastric and gastroesophageal junction adenocarcinomas (GGOJA): A single-arm multicenter phase II trial (FFCD 0901).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 154-154 ◽  
Author(s):  
Christophe Mariette ◽  
Guillaume Piessen ◽  
Carole Monterymard ◽  
Denis Pezet ◽  
Aurelie Ferru ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Tumour Response ◽  
Primary Objective ◽  
Perioperative Chemotherapy ◽  
Efficacy And Safety ◽  
Grade 3

154 Background: Whilst perioperative chemotherapy (CT) combined with radical surgery offers a survival benefit over surgery alone in GGOJA, 3-year survival still needs to be improved. The purpose of this phase II study was to evaluate the efficacy and safety of the perioperative use of cetuximab combined with 5-fluorouracil and cisplatin in operable GGOJA. Methods: Untreated operable patients with a WHO Performance Status (PS) ≤ 2 and age ≤ 75 years, with localised GGOJA received 6 cycles of intravenous Cetuximab (500mg/m²), Cisplatine (50mg/m²) and LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks. Surgery was planned 3-4 weeks after the end of neaodjuvant CT and postoperative CT planned for 6-8 weeks after surgery. The primary objective was a combined evaluation of tumoral response, assessed by centrally reviewed computed tomography, and major toxicities leading to neoadjuvant CT being discontinued. Sample size (63 patients) was calculated using Bryant and Day design (α=5%, Power=80%), expecting a rate of objective response of 45% and a percentage of patients without major toxicities of 90%. Results: 65 patients were enrolled from 2011 to 2013 with a median age of 60.5 years. 83.1% were men, 98.5% had a WHO PS<2, 30.8% had a gastric and 69.2% a junctional tumour, 28.5% had a stage II and 71.4% of patients a stage III tumour. With regard to the primary endpoint, 64 patients were evaluated, 29.7% (n=19) had an objective morphological tumour response and 95.3% (n=61) did not stop treatment prematurely due to major toxicity. 58 patients (89.2%) completed neoadjuvant CT as planned. The median duration of CT was 2.3 months and grade 3-4-5 toxicities were observed in 61.5% of patients. 60 patients (92.3%) underwent surgical resection with 24 significant complications (41.7%) and 2 postoperative deaths (3.4%). On histological analysis, 40 patients (71.4%) were non responders. Conclusions: Adding cetuximab to the neoadjuvant chemotherapy regimen in operable GGOJA is safe but does not show enough efficacy in the present study to meet the primary endpoint. Clinical trial information: NCT01360086.

Prognostic Impact of Trial-Eligibility Criteria in Patients with Metastatic Renal Cell Carcinoma

2021 ◽  
pp. 1-8
Author(s):  
Hiroki Ishihara ◽  
Hidekazu Tachibana ◽  
Hironori Fukuda ◽  
Kazuhiko Yoshida ◽  
Hirohito Kobayashi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Prognostic Impact ◽  
Eligibility Criteria

<b><i>Objective:</i></b> The aim of the study was to evaluate the prognostic impact of trial-eligibility criteria on outcome in real-world metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). <b><i>Patients and Methods:</i></b> mRCC patients treated with TKIs as first-line systemic therapy were retrospectively evaluated. The patients were determined as trial-ineligible when they met at least 1 following trial-ineligible criteria; Karnofsky performance status score &#x3c;70, hemoglobin &#x3c;9.0 g/dL, creatinine &#x3e;2.4 mg/dL (male) or &#x3e;2.0 mg/dL (female), calcium &#x3e;12.0 mg/dL, platelet &#x3c;100,000 /μL, neutrophil &#x3c;1,500 /μL, nonclear-cell histology, and brain metastasis. <b><i>Results:</i></b> Of 238 patients, 101 patients (42%) were determined as trial-ineligible. Progression-free survival (PFS) and overall survival (OS) after the TKI initiation were significantly shorter in the trial-ineligible patients than in the trial-eligible patients (median PFS: 5.53 vs. 15.8 months, <i>p</i> &#x3c; 0.0001; OS: 13.8 vs. 43.4 months, <i>p</i> &#x3c; 0.0001). Objective response rate was also significantly lower in the trial-ineligible patients (15% vs. 37%, <i>p</i> = 0.0003). Multivariate analysis further showed that the trial-eligibility was an independent factor for PFS (hazard ratio [HR]: 2.46, <i>p</i> &#x3c; 0.0001) and OS (HR: 2.39, <i>p</i> &#x3c; 0.0001). In addition, the number of trial-ineligible factors were negatively correlated with PFS and OS. <b><i>Conclusions:</i></b> In real-word, the substantial number of mRCC patients did not meet the trial-eligibility criteria, and their outcome was worse than that in the trial-eligible patients. Further studies focusing on the outcome in real-world trial-ineligible patients in the immune checkpoint inhibitor era are warranted.

Differential response rates in early-phase cancer clinical trials (EPCCT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3133-3133
Author(s):  
Rozana Abdul Rahman ◽  
Neethu Billy Graham Mariam ◽  
Hitesh Mistry ◽  
Sreeja Aruketty ◽  
Matt Church ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Sustained Response ◽  
Phase Ii Trials ◽  
Significant Difference

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for >6 mos and 7% for >12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response >6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response > 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p<0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

Anlotinib plus sintilimab in patients with recurrent advanced endometrial cancer: A prospective open-label, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5583-5583
Author(s):  
Wei Wei ◽  
Xiaohua Ban ◽  
Fan Yang ◽  
Yongwen Huang ◽  
Jibin Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Endometrial Cancer ◽  
Growth Factor ◽  
Systemic Chemotherapy ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Growth Factor Receptor

5583 Background: Endometrial cancer is one of the most common gynecologic malignancies in the world. however, the effects of systemic chemotherapy are limited. The combination of targeted therapy with immunotherapy is a new research field in the treatment of malignant tumors. Anlotinib is a novel tyrosine kinase inhibitor with highly selective inhibition effects on multi-targets, especially on vascular endothelial growth factor receptor, Platelet-derived growth factor receptor and Fibroblast growth factor receptor. Sintilimab is a highly selective, fully humanized, monoclonal antibody, which blocks the interaction between Programmed death 1 and its ligands. This research aimed to evaluate the efficacy and safety of the combination of anotinib and sintilimab in patients with recurrent advanced endometrial cancer. Methods: Patients who received at least one platinum-based systemic chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1 were considered eligible for enrollment. Sintilimab was administered intravenously (200mg，q3w); anlotinib was taken orally (12mg qd, d1-14, 21 days per cycle). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), overall survival and safety. Results: From November 2019 to to September 2020, 23 patients with a median age of 56 years (range: 37-70), FIGO stage IA (21.7%), IB (8.7%), II (4.4%), IIIA (13.1%)，IIIC (30.4%), IVB (21.7%) were enrolled. Among these participants, 22 patients were evaluable. The therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 13.6%, 63.7%, 13.6% and 9.1% respectively, yielding the ORR of 77.3% (95%CI: 58.3%-96.3%) and the DCR of 91.7% (95%CI: 79.8%-100%). ≥1 and ＜1 Combined Positive Score of PD-L1 expression were observed in 66.7% (14/21) and 33.3% (7/21) patients respectively, and the ORR was 92.9% (95%CI: 77.4%-100%) and 57.1% (95%CI: 18.4%-90.1%) in the two groups. The median time of the first response was 1.5 months (range, 0.7-12.8). The median PFS was not reached. Most of the occurring adverse events (AEs) were grade 1 or 2. Grade 3 AEs included ileus (4.3%), immune myocarditis (4.3%) immune peritonitis (4.3%), hand-foot syndrome (8.7%), neutropenia (4.3%), neutrophils decrease (4.3%), and hypertension (4.3%); Grade 4 AE was lymphocytosis (4.3%). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Anlotinib plus sintilimab showed a promising antitumor activity with a favorable toxicity profile for patients with recurrent advanced endometrial cancer. We will report more data in the future. Clinical trial information: NCT04157491.

A phase I dose-escalating study of combination S-1 and carboplatin (CBDCA) in patients with chemo-naïve advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17055-17055
Author(s):  
K. Tamura ◽  
I. Okamoto ◽  
T. Ozaki ◽  
T. Shimizu ◽  
T. Kashii ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Objective Response ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Eligibility Criteria ◽  
Level 3 ◽  
Adequate Organ Function ◽  
Level 1 ◽  
Ecog Ps ◽  
Level 2

17055 Background: S1, a novel oral fluoropyrimidine derivative, has promising results in the treatment of advanced gastric or colorectal carcinoma. Response rate/median survival time of single S1 and the combination S1 plus cisplatin for advanced NSCLC were 22.0%/309 days and 47.3%/335 days, respectively in the previous phase II. Platinum doublets including a novel active drug is a potent standard for advanced NSCLC as 1st line chemotherapy. Carboplatin has advantage of low gastrointestinal or renal dysfunction in comparison with cisplatin. The primary objective of this study was to determine the maximum tolerated dose (MTD) of combination S-1 and carboplatin, the toxicity profile and the recommend dose (RD) for a multi-center randomized trial of platinum doublets including S1. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV, no prior chemotherapy, ECOG PS 0–1, 75 > age >20, adequate organ function, and written informed consent. Pts receive carboplatin intravenously over 30 minutes on day 1, and S1 daily for 2 weeks, every 3 weeks. Results: Total 10 patients were registered (M/F: 6/4; median age:67 (37–73); Ad/Sq:7/3; IIIB/IV: 0/10 PS 0/1:3/7) Three patients were enrolled at the dose level 1 (CBDCA AUC = 5 and S1 65 mg/m2), 3 patients at level 2 (CBDCA AUC=5 and S1 80 mg/m2) and 4 patients at level 3 (CBDCA AUC=6 and S1 80 mg/m2), respectively. No DLTs (dose-limiting toxicities) occurred at both level 1 and 2. DLTs were observed in 2 out of 4 patients at level 3. One is significant delay starting of 2nd cycle caused by thrombocytopenia. One is G3 anorexia and vomiting at 1st cycle and results in stop the treatment. A total 27 courses were assessable for safety. Two pts with G3 neutropenia, 2 pts with G3 anorexia, 1 pts with G3 liver dysfunction and 1 pts with G3 infection were observed during total courses. Five out of 6 patients at Level 1 or 2 have completion of 4 cycle’s treatment. Objective response was obtained in three patients out of 10. Conclusions: MTD was level 3. RD for the future trial was Level 2 (CBDCA AUC = 5 and S1 80 mg/m2). This combination was well tolerated and produced an antitumor effect for advanced NSCLC. No significant financial relationships to disclose.

Gemcitabine (GEM) (day 1–8) plus carboplatin (CBDCA) (day 2) for the treatment of advanced non-small cell lung cancer (aNSCLC) in elderly or poor performance status (PS) patients (pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18116-18116
Author(s):  
F. Sperandi ◽  
B. Melotti ◽  
A. A. Martoni
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Objective Response ◽  
Haematological Toxicity ◽  
Dose Intensity ◽  
Poor Performance ◽  
Primary Objective ◽  
Hematological Toxicity ◽  
Poor Performance Status ◽  
Histologic Subtype

18116 Background: Several studies have demonstrated that the combination of CBDCA plus GEM according to various regimens appears as effective as cisplatin (CP) containing regimens. CBDCA plus GEM regimens are associated with more haematological toxicity (G3–4 leucopenia 17–40.6%, G3–4 neutropenia 29–75%, G3–4 thrombocytopenia 21–57% and G3–4 anaemia 5–33%), but with lower non-hematological toxicity as compared to CP-based regimens. Methods: The primary objective of this trial was the evaluation of the overall survival, while the secondary objectives were assessment of objective response and toxicity in elderly or poor PS pts. The eligible pts had previously untreated aNSCLC not suitable for CP-based chemotherapy. Pts received each at 3-week intervals GEM 1000 mg/sq on day 1 and 8 plus CBDCA area under the curve of 5 on day 2. Between April 2004 and January 2007, 54 consecutive pts were accrued in the study. Pt characteristics were: 42 (78%) males and 12 (22%) females; median age 72 years (range: 56–84 years) with 67% of pts = 70 years; median Karnofsky PS 90 (range: 50–100) with 33% of pts = 80; stage disease: IIB not suitable for surgery in 1 (2%) pt, IIIA in 5 (9%), IIIB in 10 (19%), IV in 33 (61%) and recurrent disease in 5 (9%); histologic subtype: adenocarcinoma in 30 (56%) pts, epidermoid in 11 (20%), bronchioalveolar carcinoma in 2 (4%) and other histologic subtypes in 11 (20%). Results: A median of 4 courses was administered (range 1–8). Dose- intensity was 98.7% (range 50–100%) for CBDCA and 87.2% (range 60–100%) for GEM. Objective response according to intention-to-treat analysis was as follows: 15 (28%) pts had PR, 16 (29%) had SD, 14 (27%) had PD and 9 (16%) were not assessable because lost to follow-up or too early. Median overall survival was 10 months. WHO G3 leucopenia was observed in 5 (9%) pts, G3–4 neutropenia in 15 (28%), G3 thrombocytopenia in 7 (13%) and G3 anaemia in 2 (4%). No WHO G3–4 non-hematological toxicity was observed. Conclusions: This regimen is feasible and active in elderly or poor PS pts. It can be administered in a outpatient setting because toxicity is moderate and manageable. No significant financial relationships to disclose.

A phase I/II study of pemetrexed plus cisplatin in Japanese patients with malignant pleural mesothelioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18152-18152
Author(s):  
K. Gemba ◽  
K. Yamazaki ◽  
H. Kunitoh ◽  
T. Hida ◽  
K. Nakagawa ◽  
...  
Keyword(s):  
Phase I ◽  
Performance Status ◽  
Asian Population ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Phase Iii ◽  
Vitamin Supplementation ◽  
Eligibility Criteria ◽  
Histologic Diagnosis ◽  
Level 1

18152 Background: Pemetrexed (pem) is globally used for the treatment of malignant mesothelioma (MPM) in combination with cisplatin (cis). Pharmacokinetic (PK) difference of pem/cis between Western and Asian population (pop) so far remains unknown. To investigate safety/efficacy of pem/cis therapy and PK profiles of pem/cis for Japanese (Jpn) MPM patients (pts), we designed a phase I/II study. Methods: Primary objectives in phase (Ph) I part were to determine a recommended dose (RD), and in Ph II part were to examine the efficacy of the RD and safety. PK profiles were to be analyzed as a secondary objective. A cohort of 6 pts, starting from a dose of pem 500 mg/m2 and cis 75 mg/m2 (level 1: LV1), was used in the dose-escalation Ph I. The efficacy of the RD was to be evaluated in at least 18 pts in the study. Key eligibility criteria were: histologic diagnosis of MPM incurable by surgery, no prior systemic chemotherapy, and a performance status 0–1. Under full vitamin supplementation, pem was administered as a 10-min. infusion on day 1 of a 21-day cycle, followed by cis administration as a 2-hr. infusion 30 min. after pem administration. For comparison of PK profiles, PK data of this study and a Western phase III study were analyzed by pop PK approach. Results: In Ph I, 13 pts were enrolled: 7 in LV1 and 6 in level -1 (LV-1: pem 500 mg/m2 and cis 60 mg/m2). Two dose-limiting toxicities were observed in LV1: pneumonitis and neutropenia. The RD were then determined to be LV1. In Ph II, 12 pts were enrolled in LV1. For safety, one drug-related death was reported among 25 pts due to worsening of underlying pneumonia observed before enrollment. The most common G3/4 toxicities were neutropenia and hemoglobin decrease. For efficacy, a partial response was achieved for 7 of 19 pts who received LV1. Response rate was 36.8% (95% CI: 16.3- 61.6). PK profiles of pem/cis in Jpn pts were similar to those in Western. The results of other secondary objectives, e.g., progression-free survival, QOL, and pulmonary function test, will be presented in the conference. Conclusions: The profiles of efficacy/safety/PK shown in this study are almost comparable to those in Western pts, and indicate that pem/cis therapy will be a promising therapy for Jpn MPM pts. No significant financial relationships to disclose.

MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
T. J. Hobday ◽  
J. Rubin ◽  
K. Holen ◽  
J. Picus ◽  
R. Donehower ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Eligibility Criteria ◽  
Grade 3

4504 Background: Treatment options for metastatic NET, including islet cell carcinoma (ICC) and carcinoid tumor (CT), are limited. These tumors frequently express vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor receptor-β (PDGFR-β). Sorafenib, a small-molecule inhibitor of the VEGFR-2 and PDGFR-β tyrosine kinase domains, is a rational targeted therapy to evaluate in NET. Methods: Eligibility criteria included: ECOG PS = 2, = 1 prior chemotherapy, good organ function and signed informed consent. Prior interferon and prior or concurrent octreotide at a stable dose were allowed. Pts unable to take oral medications, with uncontrolled hypertension or with symptomatic coronary artery disease were excluded. Pts received sorafenib 400 mg po BID. Primary endpoint was response by RECIST in two cohorts (ie, CT and ICC) using separate 2-stage phase II designs. Results: 93 pts were enrolled: (50 CT, 43 ICC). For pts evaluable for the primary endpoint, 4 of 41 (10%) CT pts and 4 of 41 (10%) ICC pts had a PR. There were 3 minor responses (MR = 20–29% decrease in sum of target lesion diameters) in CT pts and 9 MRs in ICC pts for PR+MR rate of 17% for CT pts and 32% for ICC pts. For pts evaluable, 6-month progression-free survival was observed in 8/20 CT and 14/23 ICC pts. Grade 3–4 toxicity occurred in 43% of pts, with skin (20%), GI (7%) and fatigue (9%) most common. Translational studies from tumor tissue will be presented. Conclusions: Sorafenib at 400 mg po BID has modest activity in metastatic neuroendocrine tumors, with frequent grade = 3 toxicity. Supported by NOI CM6225. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document