FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
David I. Quinn ◽  
Daniel Peter Petrylak ◽  
Joaquim Bellmunt ◽  
Andrea Necchi ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Activating Mutations ◽  
Stage Iv Disease ◽  
Dna Alterations ◽  
Grade 3 ◽  
Muscle Invasive

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.

Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients (pts) with stage IV non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8014-8014
Author(s):  
C. Manegold ◽  
J. Vansteenkiste ◽  
F. Cardenal ◽  
W. Schütte ◽  
P. Woll ◽  
...  
Keyword(s):  
Survival Rate ◽  
Tumor Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
One Year

8014 Background: Cilengitide (EMD 121974) is the most advanced compound in clinical development of a new class of oncology drugs, the integrin inhibitors. Integrins (heterodimeric transmembrane receptors) play key roles in cell interactions. Cilengitide selectively inhibits the cell-surface integrins αVβ3 and αVβ5 on activated endothelial cells during angiogenesis and on tumor cells. Methods: Multicenter, open-label, randomized, phase II study in 140 pts with relapsed stage IV NSCLC. Pts received 1 of 3 cilengitide doses (240 [n=35], 400 [n=35], or 600 [n=36] mg/m2) twice weekly or docetaxel 75 mg/m2 (n=34) once every 3-week cycle for 6 months. Responding pts could continue cilengitide for up to 1 year. Primary endpoint: progression-free survival (PFS). Results: Median age (range) was 60 (33–80) years; 94 pts were male (67%); 83% of pts had KPS ≥80%. Median PFS (95% CI) was 54 (43–64), 63 (53–66), 63 (42–67), and 67 (61–123) days for cilengitide 240, 400, 600, and docetaxel 75 mg/m2, respectively. Median OS (95% CI) was 173 (81–197), 117 (92–209), 181 (90–326), and 194 (135–298) days, respectively. One-year survival rate (95% CI) was 13% (1–24%), 13% (0–26%), 29% (12–37%), and 27% (10–43%), respectively. Survival was similar with cilengitide 600 mg/m2 and docetaxel 75 mg/m2: median OS 181 versus 194 days and 1-year survival rate (95% CI) 29% (12–37%) versus 27% (10–43%). Five docetaxel pts (15%) had a partial response. Most pts (98%) had ≥1 adverse event (AE). Most common AEs were dyspnea (33%), nausea (30%), tumor progression (29%), and cough (23%). Dyspnea and tumor progression were more common with cilengitide than with docetaxel. Grade 3/4 treatment-related AEs were more common with docetaxel (n=13, 41%) than cilengitide 240 (n=2, 6%), 400 (n=4, 11%), or 600 (n=4, 11%) mg/m2. For cilengitide, these were nausea, chest pain, dyspnea, and fatigue. Conclusions: PFS in the docetaxel group was greater than that of cilengitide at all doses. However, cilengitide monotherapy at a dose of 600 mg/m2 showed similar OS to docetaxel and better tolerability. Combination studies with standard chemotherapy and cilengitide are warranted. [Table: see text]

Phase II randomized trial of radiotherapy (RT), cetuximab (E), and pemetrexed (Pem) with or without bevacizumab (B) in locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6043-6043 ◽  
Author(s):  
Athanassios Argiris ◽  
James Ohr ◽  
Greg J. Kubicek ◽  
Uma Duvvuri ◽  
Dwight Earl Heron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Stage Iii ◽  
Community Practice ◽  
History Of ◽  
Grade 3

6043 Background: We previously developed a novel regimen by the addition of Pem to RT and E (Ann Oncol 2011;22:2482). The current study evaluated PemE in the phase II setting and assessed the addition of B, an anti-VEGF monoclonal antibody, to PemE based on promising data with Pem/B (JCO 2011;29:1140) and E/B (Ann Oncol 2013;24:200) in recurrent/metastatic SCCHN. Methods: Patients (pts) with previously untreated stage III/IV SCCHN of the oropharynx, larynx or hypopharynx, performance status (PS) 0-1, no history of bleeding, and adequate laboratory parameters were randomized after stratification for PS, stage and site to: RT 2 Gy/day to 70Gy, E 250mg/m2 weekly, after a loading dose of 400 mg/m2 1 week prior starting RT, and Pem 500mg/m2 every 21 days x 3 cycles (arm A, PemE), or the same regimen plus B 15mg/kg every 21 days x 3 cycles during RT followed by B maintenance x 8 cycles (arm B, B-PemE), with antibiotic prophylaxis. The primary endpoint was progression-free survival (PFS) with a target of 64% at 2 years; planned sample size was 80. Results: 79 pts were randomized of whom 77 were eligible and analyzable (arm A/B:36/41); oropharynx 65/larynx 12; HPV+ 38/HPV- 15/HPV unknown 24; stage IV 54/stage III 23. 31 pts were enrolled in community centers. Treatment delivery of E and Pem was similar between arms: E, median number of doses 8 (range, 5-11); Pem 3 (2-3); and B 3 (1-3). 5 deaths occurred: 3 due to progression; 1 from unknown cause; 1 pt died from hemoptysis after bronchoscopy within 4 weeks of the 8th cycle of B leading to elimination of B maintenance after the 6th pt was enrolled. 9 pts (2 HPV+) progressed. With a median follow-up of 18 months, the 2-year PFS was 81% vs 87% and the 2-year overall survival (OS) was 96% vs 86% for arm A vs B. Grade 3/4 acute toxicities for arm A vs B (N=59) : dermatitis 3/1 vs 4/1; mucositis 13/2 vs 13/0; neutropenia 7/4 vs 7/3; rash 6/1 vs 8/1; fatigue 1/0 vs 3/0; weight loss 2/0 vs 5/0. Conclusions: Both regimens are feasible in academic and community practice settings with expected toxicities. Preliminary efficacy results are very promising and better than projected, however, the addition of B does not appear to improve outcomes. Clinical trial information: NCT00703976.

Regomune: A phase II study of regorafenib + avelumab in solid tumors—Results of the biliary tract cancer (BTC) cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Sophie Cousin ◽  
Carine A. Bellera ◽  
Jean Philippe Guégan ◽  
Thibault Mazard ◽  
Carlos A. Gomez-Roca ◽  
...  
Keyword(s):  
Phase Ii ◽  
Adaptive Design ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Clinical Activity ◽  
Open Label

4096 Background: Regorafenib (R) has shown promising efficacy in patients (pts) with BTC refractory to standard chemotherapy. Anti-PD1/PD-L1 antibodies have only limited clinical activity. Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical solid tumor models. Methods: This is a single-arm open-label multicentric phase II trial (Bayesian adaptive design) assessing the efficacy and safety of R (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in BTC pts. The primary endpoint was the objective response rate under treatment, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Nov. 2018 and Nov. 2019, 34 BTC pts were enrolled in 4 centers. Median age was 63 (range 36 – 80). Median follow-up was 9.8 months. Median number of previous treatment lines for metastatic or locally advanced disease was: 2 (range 1 – 4). Twenty-nine (85.3%) pts experienced at least 1 dose modification or treatment interruption of R or A due to an adverse event (AE) related to the treatment. The most common grade 3/4 AEs were : Hypertension (17.6%), Fatigue (14.7%), and maculo-papular rash (11.8%). No death was related to the treatment. Among the 29 pts with at least one imaging tumor assessment, 4 (13.8%) achieved a partial response, and 11 (37.9%) demonstrated stable disease including 10 (34.5%) pts with tumor shrinkage. Fourteen pts (48.3%) had progressive disease. The median PFS and OS were 2.5 months (95%CI 1.9 – 5.5) and 11.9 months (95%CI 6.2 – NA) respectively. Baseline tumor samples were available for 27 pts. High IDO and PD-L1 expression at baseline was associated with better outcome. Conclusions: The R+A combination is associated with significant anti-tumor activity with promising survival rates in this heavily pre-treated population. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: A phase Ib/II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 312-312
Author(s):  
Mitesh J. Borad ◽  
Li-Yuan Bai ◽  
Ming-Huang Chen ◽  
Joleen M. Hubbard ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Almost All

312 Background: Silmitasertib (CX-4945), an oral small molecule inhibitor of casein kinase 2 (CK2), has exhibited preclinical antitumor activity and strong synergism with gemcitabine + cisplatin. We investigated the safety and efficacy of silmitasertib in combination with gemcitabine + cisplatin in patients with unresectable cholangiocarcinoma (CCA). Methods: S4-13-001 is a multicenter, open-label, phase Ib/II study of silmitasertib in combination with gemcitabine + cisplatin in patients with locally advanced or metastatic CCA. The phase Ib portion included dose-escalation, expansion, and exploratory cohorts of silmitasertib with doses ranging from 200 to 1000 mg bid (6 days for the escalation/expansion cohorts and 10 and 21 days’ continuous dosing for the exploratory cohorts). In the phase II portion patients received silmitasertib 1000 mg bid for 10 days in combination with gemcitabine + cisplatin on days 1 & 8 over a 21-day cycle. In this interim analysis, we present findings from the combined population of patients from the phase Ib and II portions of the study. Response to treatment was assessed by RECIST v1.1 every 6 weeks. Primary efficacy outcome measure was progression-free survival (PFS). ClinicalTrials.gov (NCT02128282). Results: A total of 87 patients were enrolled and received silmitasertib in the phase Ib (n=50) and phase II (n=37) portions of the study. Of these, 55 patients were evaluable for efficacy with details as follows: median PFS 11.1 (95% CI 7.6–14.7) months; median overall survival (OS) 17.4 (95% CI 13.4–25.7) months; overall response rate (ORR) 32.1%; and disease control rate (DCR) 79.3%. Almost all patients (79/87; 90.8%) evaluable for safety reported ≥1 treatment-related adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib were diarrhea (65.5%), nausea (50.6%), vomiting (33.3%), fatigue (31.0%), and anemia (21.8%). The most common grade ≥3 TEAEs were diarrhea (13.8%), neutropenia (11.5%), nausea (9.2%), anemia (8.0%), and thrombocytopenia (8.0%). Eleven patients (12.6%) discontinued treatment due to TEAEs. Conclusions: Silmitasertib in combination with gemcitabine + cisplatin yields promising preliminary evidence of efficacy in patients with locally advanced or metastatic CCA. Based on these data a randomized phase III trial is planned. Clinical trial information: NCT02128282.

Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8560-8560 ◽  
Author(s):  
D. G. Perez ◽  
V. Suman ◽  
T. Amatruda ◽  
M. Gornet ◽  
R. Morton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Unresectable Stage ◽  
Full Study ◽  
Grade 3 ◽  
Endothelial Growth Factor ◽  
Stage Iv Melanoma

8560 Background: In patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets vascular endothelial growth factor (VEGF) might be able to control tumor growth and progression much more effectively than chemotherapy alone. Methods: A two-stage phase II clinical trial was conducted in patients with unresectable stage IV melanoma to assess the anti-tumor activity and toxicity profile of the combination of paclitaxel (80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle), carboplatin (AUC = 6 IV on day 1) and bevacizumab (10 mg/kg IV on days 1 and 15). The primary end point of the study was the 8-week progression-free survival rate (PFS). Enrollment to the second stage of the study was opened if 8 or more of the first 20 patients enrolled remained progression-free at 8 weeks. Eligible patients had measurable disease by RECIST criteria, a performance status (PS) of 0–2 and acceptable pre-registration organ function. Exclusion criteria included: brain metastases, significant recent bleeding, uncontrolled hypertension and ongoing anticoagulation. The study opened in February 2006 and completed full study accrual in August 2006. Data from the 20 patients enrolled in the first stage are presented here. Results: Patients (60% male) had a median age of 63 and had a good performance status (85% had PS of 0). M1c disease was present in 45% of patients and 35% had undergone previous chemotherapy for stage IV melanoma (50% prior immunotherapy). Only 6 patients did not complete more than 2 cycles of chemotherapy due to refusal (3), desire for alternative treatment (1) or progression (2). Median follow-up among the 15 patients still alive was 5.5 months (range: 6 weeks - 9 months). The 8-week PFS rate was 70% (14/20). The median time to progression was 163 days. One partial response was observed. There were 3 disease-related deaths at 65, 120 and 190 days post-registration. The most common toxicities were neutropenia (95%; 45% = grade 3), anemia (95%; 15% = grade 3), fatigue (90%; 5% = grade 3), leukopenia (85%; 25% = grade 3), and thrombocytopenia (75%; 5% = grade 3). Conclusions: The combination of paclitaxel, carboplatin and bevacizumab appears to be well tolerated and clinically active in patients with stage IV melanoma. No significant financial relationships to disclose.

Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
M. H. Moehler ◽  
P. Thuss-Patience ◽  
D. Arnold ◽  
W. Grothe ◽  
A. Stein ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Response Assessment ◽  
Metastatic Gastric Cancer ◽  
Phase Ii Trials ◽  
Grade 3 ◽  
Ecog Ps

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19062-e19062
Author(s):  
J. R. Fischer ◽  
F. Griesinger ◽  
T. Fink ◽  
E. Buchholz ◽  
T. Salm ◽  
...  
Keyword(s):  
Phase Ii ◽  
Partial Remission ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Benefit Risk Assessment

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]

Randomized phase II study of S-1/CDDP plus TSU-68 versus S-1/CDDP in patients with advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 72-72
Author(s):  
Kensei Yamaguchi ◽  
Wasaburo Koizumi ◽  
Hisashi Hosaka ◽  
Yasutaka Takinishi ◽  
Norisuke Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Open Label ◽  
Parallel Group ◽  
Common Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

72^ Background: Gastric cancer (GC) is the second leading cause of cancer death in Japan as well as globally. Effective treatment of GC remains a therapeutic challenge. Although in the AVAGAST trial, bevacizumab was found to offer no survival benefit. Angiogenesis continues to be the standard treatment for GC, and thus, clinical trials on many anti-angiogenic drugs have been conducted. TSU-68 (orantinib) is an oral, angiokinase inhibitor targeting the vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. The present study evaluated the progression-free survival (PFS) and pharmacokinetics (PK) of TSU-68 in combination with Japanese standard S-1 and cisplatin (S-1/CDDP) in patients with advanced GC. Methods: In this open-label, multicenter, randomized, controlled, parallel-group, phase II trial, patients were randomized to Arm A (S-1/CDDP) or Arm B (TSU-68 plus S-1/CDDP). All patients received oral S-1 (40-60 mg/m2) twice daily for 21 days followed by a 14 day rest plus intravenous CDDP (60 mg/m2) on Day 8, repeated every 35 days. In Arm B pts received oral TSU-68 (400 mg/dose) alone, twice daily by addition 35 days. The primary endpoint was PFS. Results: In total, 93 patients were enrolled. For Arm A [male:female ratio], n=47 [35:11]; Arm B, n=45 [30:15]; the respective median age was 63.5 and 62.0 years. The median PFS was 7.0 and 6.8 months in Arms A and B, respectively (HR, 1.23; 95%CI, 0.74 to 2.05; P=0.425); the respective response rates were 56.5% and 62.2%. The most common grade 3/4 toxicities were neutropenia (Arms A and B, 34.8% and 31.1%) and hemoglobin (Arms A and B, 26.1% and 48.9%). There were no differences in other toxicities between the 2 arms, both treatments were tolerated, and no treatment-related deaths were observed. In the PK study, although Arm B had a significantly lower plasma exposure to FT, CDHP, and Oxo compared to Arm A, the exposure to 5-FU was not different between the 2 arms. The exposure to CDDP in Arm B was significantly but slightly lower than that in arm A. Conclusions: Thus,TSU-68 plus S-1/CDDP therapy did not prolong PFS of patients with advanced GC as compared with S-1/CDDP. Clinical trial information: JapicCTI-101327.

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