Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in metastatic colorectal cancer (mCRC) patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
Pilar Garcia Alfonso ◽  
Manuel Chaves-Conde ◽  
Andres Munoz ◽  
Antonia Salud ◽  
Carlos Garcia-Giron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Kras Status

501 Background: XELIRI regimen biweekly (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. Bevacizumab provides significant clinical benefits in previously treated patients with mCRC. On this basis, the aim of this study is to evaluate the efficacy and safety of this combination. Methods: Multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (iri) (175mg/m2 d1 q2w) + capecitabine (xel)(1,000mg/m2bid d 2-8) + bevacizumab (bev) (5mg/kg, d1 q2w). Results: 77 patients (p) were evaluated (66.2%, male) with a median age of 65.1 years (41.1-81.1). ECOG performance status was ≤1 in 96.1%. Primary tumor locations were: colon (53.2%), rectum (31.2%), and rectum/colon (15.6%). 27 p (35.1%) received adjuvant chemotherapy. Metastases were detected in liver (62.3%) and lung (54.5%). Mean time in treatment was: 7.1±4.9 months and median of cycles administered was 12(1-43). Median relative dose intensity was 89% for xel and bev and 85% for iri. Best response confirmed were: complete response (5.2%), partial response (32.5%), stable disease (46.8%). After a median of follow-up of 23.3 (0.4-39.6) months, median overall survival (OS) and progression free survival (PFS) was 24.8 and 11.8 months respectively. Analysis on Kras status was done in 71 p. There were no significant differences in OS or in PFS between WT and MUT p. 17 p (22.1%) underwent salvage surgery, 12 of whom had an R0 resection. The most frequent G3-4 toxicities were: diarrhea (18.2%), asthenia (16.9%), pulmonary embolism (13%; in eight of 10 p were asymptomatic), neutropenia (10.4%), febrile neutropenia (6.5%) and HFS (5.2%). Three treatment related deaths were reported (2 cases of multi-organ failure, and 1 case of intestinal perforation). Conclusions: Bevacizumab combined with biweekly XELIRI is an active first-line regimen for mCRC treatment with a feasible and manageable safety profile. Bevacizumab treatment efficacy was independent on Kras status. Clinical trial information: NCT00875771. [Table: see text]

Phase II efficacy and safety study of nintedanib versus sunitinib in previously untreated renal cell carcinoma (RCC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4506-4506 ◽  
Author(s):  
Tim Eisen ◽  
Yaroslav Shparyk ◽  
Robert Jones ◽  
Nicholas James MacLeod ◽  
Graham Temple ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Qtc Interval ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Interval Change ◽  
First Line Therapy

4506 Background: Sunitinib (S) is established as a standard first-line therapy for patients (pts) with advanced RCC. However, treatment can be limited by the occurrence of drug-related adverse events (AEs). This Phase II study assessed the efficacy and safety of nintedanib (N) – a potent, triple angiokinase inhibitor of VEGFR-1–3, PDGFR-α/β, and FGFR-1–3, as well as RET and Flt3 – vs S in previously untreated pts with RCC. Methods: Ninety-nine eligible pts (96 of whom were treated) with advanced, unresectable/recurrent clear cell RCC, an ECOG performance status of 0–1, and no prior systemic therapy were randomized 2:1 to receive N 200 mg twice daily (n=64; given in 4-week cycles) or S 50 mg once daily (n=32; 4 weeks on, 2 weeks off schedule). Treatment continued until disease progression or unacceptable drug-related AEs. Primary endpoints were progression-free survival at 9 months (PFS-9) and, in N-treated pts only, QTc interval change (baseline to day 15). Secondary endpoints included PFS, objective response rate (ORR; RECIST 1.1), overall survival (OS), time to progression (TTP), time to treatment failure (TTF), and AEs. Results: Baseline characteristics were balanced between the arms. PFS-9 was not statistically significantly different between N- and S-treated pts (43 vs 45%; p=0.85). There were also no statistically significant differences between N and S with regard to PFS (median: 8.44 vs 8.38 mo; hazard ratio: 1.16; 95% CI: 0.71–1.89; p=0.56), confirmed ORR (18.8 vs 31.3%; p=0.19), OS (median: 20.37 vs 21.22 mo; p=0.63), TTP (median: 8.48 vs 8.54 mo; p=0.52), and TTF (median: 8.41 vs 8.36 mo; p=0.46). Grade ≥3 AEs occurred in 47% of N-treated pts and 56% of S-treated pts. Common AEs (all grades; N vs S) included diarrhea (61 vs 50%), nausea (38 vs 34%), fatigue (both 25%), and vomiting (16 vs 22%). Dermatologic AEs (8 vs 47%) were less frequent with N than S. There was no increase from baseline in QTc >60 ms on days 1 or 15 in N-treated pts, and there was no relationship between N exposure and QT interval change. Conclusions: N demonstrated similar efficacy to S and had a manageable safety profile, including a lower incidence of dermatologic AEs vs S. In addition, N was not associated with QT prolongation. Clinical trial information: NCT01024920.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

An open, multicenter, phase II clinical trial to evaluate efficacy and safety of S-1 split cisplatin in patients with advanced gastric cancer (AGC): HGCSG0702—Safety analysis.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 121-121
Author(s):  
Ichiro Iwanaga ◽  
Satoshi Yuki ◽  
Hiraku Fukushima ◽  
Atsushi Ishiguro ◽  
Takenori Takahata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Rest Period ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
High Dose ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Efficacy Analysis ◽  
Multicenter Phase

121 Background: From the results of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with AGC in Japan. However, many facilities are forced hospitalization of hydration upon administration of high dose Cisplatin (60mg/m2). Therefore, in Hokkaido Gastrointestinal Cancer Study Group (HGCSG), to investigate the safety and efficacy, we conducted a multicenter phase II clinical trials of S-1 plus split cisplatin as a therapeutic strategy that can be administered in the outpatient. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40-60 mg depending on patients body surface area) was given orally, twice daily for 3 consecutive weeks, and 30 mg/m2 cisplatin was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and duration of hospitalization. Results: Between Mar 2008 and Mar 2012, 40 pts were enrolled. Patients characteristics were as follows: median age 63 years (range 41-75), Male: female 30:10, PS 0:1 33:7. Median no. of cycles was 3. The most common non-hematological adverse events (AE) were anorexia (70%), nausea (60%), fatigue (60%) and diarrhea (48%) and hematological AE were anemia (88%), neutropenia (83%), leukocytopenia (68%) and thrombocytopenia (60%). The main grade 3-4 AE were neutropenia (40%), anemia (30%), anorexia (30%) and fatigue (15%). These AE were as expected. The median dose intensity of S-1 was 270mg/m2/week (relative dose intensity (RDI) 80%), and cisplatin was 10.1mg/m2/week (RDI 84%). These toxicities were tolerable and manageable. No treatment-related death was observed. Conclusions: We conclude that this S-1 plus split cisplatin regimen was well tolerated in the treatment of AGC, and most patients could be administered in the outpatient. We are planning the final efficacy analysis for February 2013.

scholarly journals A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma

2021 ◽  
Author(s):  
Katja Werlenius ◽  
Giuseppe Stragliotto ◽  
Michael Strandeus ◽  
Malin Blomstrand ◽  
Helena Carén ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Open Label ◽  
Serious Adverse Events ◽  
Significant Difference

Abstract Background There is an urgent need for effective treatments against glioblastoma (GBM). In this trial we investigated the efficacy and safety of an adoptive cell-based immunotherapy. Methods Patients with newly diagnosed GBM were recruited at four study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were survival and safety of ALECSAT. Results Sixty-two patients were randomized to either RT and TMZ alone (n=22) or RT and TMZ with ALECSAT (n=40). Median age was 57 years (range 38-69), 95% of the patients were in good performance status (WHO 0-1). There was no significant difference between the study arms (SOC vs. ALECSAT + SOC) in PFS (7.9 vs. 7.8 months; HR 1.28; 95% CI 0.70, 2.36; P=0.42), or in median overall survival (OS) (18.3 vs. 19.2 months; HR 1.16, 95% CI 0.58, 2.31; P=0.67). The treatment groups were balanced in terms of serious adverse events (52.4% vs. 52.5%), but adverse events ≥ grade 3 were more common in the experimental arm (81.0% vs. 92.5%). Conclusion Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.

Efficacy and safety of bevacizumab (BEV)-based combination regimens in patients with metastatic colorectal cancer (mCRC): Randomized phase II study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD 13/0503 study)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4086-4086
Author(s):  
M. Ducreux ◽  
A. Adenis ◽  
J. Mendiboure ◽  
E. François ◽  
E. Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Free Survival ◽  
First Line Therapy ◽  
Number Of Cycles ◽  
Combination Regimens

4086 Background: The combination of BEV and chemotherapy is highly effective in patients with mCRC and improves response rate, progression-free survival and overall survival compared with chemotherapy alone. This randomized non-comparative phase II trial evaluated the efficacy and safety of BEV in combination with either XELIRI or FOLFIRI as first-line therapy for mCRC. Methods: Patients were eligible for inclusion in this study if they had histologically proven measurable mCRC, were aged 18–75 years, and had an ECOG performance status (PS) of 0–2. Patients were treated with 8 cycles of XELIRI (irinotecan 200 mg/m2 on Day 1 and capecitabine 1000 mg/m2 bid on Days 1–14) + BEV 7.5 mg/kg on Day 1, every 3 weeks or 12 cycles of FOLFIRI (irinotecan 200 mg/m2 on Day 1 + 5-fluorouracil (5-FU) 400 mg/m2 + folinic acid 400 mg/m2 on day 1 followed by 5-FU 2400 mg/m2 via 46-h infusion) + BEV 5 mg/kg on day 1, every 2 weeks. BEV was continued to disease progression. Patients aged ≥65 years received a lower daily dose of capecitabine (800 mg/m2 bid). The primary endpoint was crude progression-free survival (PFS) at 6 months. Results: In total, 145 patients were entered in the study between March 2006 and January 2008; 72 patients received BEV + XELIRI and 73 patients received BEV + FOLFIRI (male 64%/48%; median age 61/61 years; 35/36% aged >65 years). Preliminary results from the first 6 months of follow-up are reported here. A total of 491/783 cycles was administered, 63%/67% receiving at least the initially planned number of cycles (8 cycles for BEV + XELIRI and 12 for BEV + FOLFIRI). Main results are given in the table . Conclusions: This randomized non-comparative study has shown that BEV + XELIRI and BEV + FOLFIRI are similarly effective treatments for patients with mCRC, with manageable toxicity profiles. Results with updated follow-up will be presented at the Meeting. [Table: see text] [Table: see text]

Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8028-8028
Author(s):  
R. Jotte ◽  
P. Conkling ◽  
C. Reynolds ◽  
L. Klein ◽  
J. F. Fitzgibbons ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2nd-line ED-SCLC sensitive to 1st-line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1st-line platinum-based chemotherapy (recurrence or progression ≥90 days from 1st-line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m2/d (d, 1–3) or IV topotecan 1.5 mg/m2/d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p<0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2nd-line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]

Phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in patients with unresectable metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 611-611 ◽  
Author(s):  
Takeshi Kato ◽  
Tomohiro Nishina ◽  
Kentaro Yamazaki ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Prolonged Treatment ◽  
Efficacy And Safety ◽  
Resection Rate ◽  
Ecog Performance Status ◽  
Grade 3

611 Background: The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) had promising activity with well-tolerated toxicities compared to mFOLFOX6 (Ojima et al, ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR=0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study. Methods: The inclusion criteria were; 1) histologically proven adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment for metastatic disease, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week and L-OHP (85 mg/m2), and BV (5 mg/kg) on day 1, every 2 weeks. The primary endpoint was the response rate (RR). Results: From October 2009 to April 2010, 31 pts were enrolled, and 29 pts were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles. RR assessed by the independent review committee was 86.2 % (CR: 0 pts, PR: 25 pts), and disease control rate (DCR) was 100%. The median PFS assessed by investigators was 12.5 months, while further follow up is ongoing. One year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m2 (range 330-1735 mg/m2). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 13 pts, and metastatectomy by tumor regression in 6 pts. The resection rate was 17.2 %. Conclusions: SOL+BV showed promising activity with high RR, DCR, PFS and resection rate with well tolerated toxicities in pts with unresectable mCRC. This trial was supported by Taiho Pharmaceutical CO.,LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).

Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8558-8558 ◽  
Author(s):  
Luana Calabro ◽  
Aldo Morra ◽  
Diana Giannarelli ◽  
Giovanni Amato ◽  
Erica Bertocci ◽  
...  
Keyword(s):  
Phase Ii ◽  
Liver Toxicity ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Primary Objective ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status

8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.

Efficacy and safety of axitinib (AG-013736; AG) in patients (pts) with advanced non-small cell lung cancer (NSCLC): A phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7507-7507 ◽  
Author(s):  
J. H. Schiller ◽  
T. Larson ◽  
S. I. Ou ◽  
S. A. Limentani ◽  
A. B. Sandler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tyrosine Kinases ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Single Agent ◽  
Efficacy And Safety ◽  
Duration Of Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Eligibility Criteria

7507 Background: A correlation between vascular endothelial growth factor (VEGF), microvessel density, and prognosis has been reported in pts with NSCLC. AG is a small molecule inhibitor of the receptor tyrosine kinases, with picomolar potency against VEGFR 1, 2 and 3 and nanomolar potency against PDGFR-β and KIT. This is an open-label, multicenter phase II study examining the efficacy and safety of AG in pts with advanced NSCLC. Methods: Pts with stage IIIB or metastatic NSCLC received AG 5 mg BID. Eligibility criteria included measurable disease and ECOG performance status of 0 or 1. A Simon 2-stage minimax design was used with 18 pts in the first stage plus an additional 14 in the second stage if 1/18 pts responded. The primary endpoint was response rate (RR) according to RECIST. Results: A total of 32 pts were enrolled: median age was 66 yrs (39–80); histologies were adenocarcinoma (75%), squamous cell carcinoma (9%), and not otherwise specified (16%); 56% male/44% female; 72% received prior chemotherapy, 47% prior surgery, 47% prior radiotherapy, 9% investigational therapy, 3% immunotherapy, and 13% were treatment-naïve. Mean duration of treatment was 93 days (1–271). Three (9.4%) investigator confirmed responses were reported with a 95% confidence interval (CI) of 2, 25. Median duration of response was 9.4 months (mo). Median survival was 12.8 mo (95% CI: 9.9 mo, undefined) and progression-free survival was 5.8 mo (95% CI: 3.8 mo, 10.2 mo). 26 (81%) pts discontinued treatment: lack of efficacy 19 pts (59%), adverse events 5 pts (16%), death 1 pt (3%), and withdrawal of consent 1 pt (3%). Grade 3/4 toxicities (=5%) were fatigue (22%), diarrhea (6%), hypertension (6%) and hyponatremia (6%). Conclusions: AG demonstrates single- agent activity in pts with advanced NSCLC. Therapy is well tolerated with manageable toxicity in this population. Further investigation in this setting is warranted. [Table: see text]

Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6022-6022 ◽  
Author(s):  
H. D. Brooks ◽  
B. Glisson ◽  
C. Lu ◽  
A. Sabichi ◽  
F. Johnson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Open Label ◽  
Ecog Performance Status ◽  
Open Label Phase ◽  
Grade 3 ◽  
Efficacy Parameters

6022 Background: Dasatinib is a potent inhibitor of src-family kinases, ephA2, PDGFR, Abl, and c-kit. A single-center, open-label, phase II trial was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of dasatinib in recurrent or metastatic HNSCC. Methods: Pts with measurable disease by RECIST, who received 0 or 1 prior regimen for recurrent or metastatic HNSCC with an ECOG performance status 0–1 and tumor tissue appropriate for IHC and FISH were eligible. Dasatinib 100 mg bid was given for 28-day cycles. Primary endpoints were 12-wk progression-free survival (PFS) and objective response rate (ORR). Pts who took at least 1 dose of dasatinib and who died or left study before 12 wks were counted as progressive disease (PD). A 2 stage design, closure after accrual of 15 pts was required if PFS was 45% or less and ORR was 0. Otherwise, planned accrual was 35. Response was assessed at 4 and 12 wks. PK was studied in pts receiving dasatinib per PEG. Biomarkers relevant to Src pathway were planned in tissue and blood. Results: Fifteen pts were accrued. To date, 13 pts are evaluable for response, and 15 pts for toxicity. No grade 3/4 hematologic toxicities were noted. Grade 2–4 nonhematologic toxicities(n): pleural effusion(2), nausea/vomiting(2), dehydration(1), diarrhea(1), dyspnea(1). Toxicity led to hospitalization of 4 pts and drug discontinuation in 5 pts. ORR was 0. One pt was stable at 12 wks (PFS: 7.6%). This pt stopped drug at 15 wks due to toxicity, but also had PD. One pt died on study and cause was deemed unlikely related. Conclusions: Dosed at 100mg bid, dasatinib led to a characteristic toxicity profile in this pt population. Rates of hospitalization and discontinuation for toxicity were fairly high. Final efficacy parameters are pending evaluation of 2 pts. Evaluation of PK and tissue/blood biomarkers is ongoing. No significant financial relationships to disclose.

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