Gefitinib in combination with paclitaxel (P) and carboplatin (C) as second-line therapy for ovarian, tubal or peritoneal adenocarcinoma: Final results of a phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5566-5566 ◽  
Author(s):  
P. Pautier ◽  
F. Joly ◽  
P. Kerbrat ◽  
P. Bougnoux ◽  
P. Fumoleau ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Resistant Refractory ◽  
Platinum Sensitive ◽  
Egfr Expression

5566 Background: High EGFR expression occurs in 35–70% of primary ovarian tumors and is often associated with poor prognosis. This Phase II, open-label, non-comparative multicenter study investigated the efficacy and tolerability of gefitinib (Iressa) in combination with paclitaxel (P) and carboplatin (C) for second-line treatment of patients (pts) with ovarian, tubal or peritoneal adenocarcinoma. Methods: Women (>18 years) with platinum-resistant/refractory (relapsed <6 months after first-line platinum-based and P chemotherapy), or platinum-sensitive (relapsed >6 months) disease were enrolled. Pts received gefitinib (500 mg/day), P (175 mg/m2) and C (AUC 5) every 3 weeks for 6–8 cycles, after which pts could continue to receive gefitinib. The primary endpoint was objective response rate (ORR) assessed using RECIST or Rustin criteria. Results: Sixty-eight pts (26 resistant/refractory and 42 sensitive) were enrolled (median age [range]: 57 [34–72] years; ECOG performance status 0/1/2: 41/26/1). ORR and disease control rates were 19.2% and 69.2%, respectively, for resistant/refractory; and 61.9% and 81.0%, respectively, for sensitive pts (see table ). Grade 3/4 toxicities (in =10% pts) were neutropenia (59%), diarrhea (25%), leukopenia (22%), anemia (13%), and acne (13%). Two myelodysplastic syndromes (MDS) and one acute biphenotypic leukemia were observed during treatment. Another pt developed MDS 34 months after study treatment discontinuation. Conclusions: Gefitinib (Iressa) in combination with P and C has promising activity as second-line treatment for ovarian, tubal or peritoneal adenocarcinoma and is generally well tolerated. The hemopathies are under further investigation. [Table: see text] No significant financial relationships to disclose.

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.

A phase II study of second-line S-1/CPT-11+bev for advanced colon cancer (NCCSG04): Subset analysis by K-ras, EGFR, UGT1A1, and previous bevacizumab.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 564-564
Author(s):  
Yasumasa Takii ◽  
Kouichi Furukawa ◽  
Satoshi Maruyama ◽  
Toshiyuki Yamazaki ◽  
Atsushi Nishimura ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
Negative Case ◽  
Wild Group

564 Background: We planned a phase II trial to evaluate the efficacy and safety of irinotecan, S-1, and bevacizumab (IRIS/Bev) as second-line therapy for patients with metastatic colorectal cancer (mCRC). The result of this study was reported an active and generally well-tolerated 2nd-line treatment for mCRC (Takii et al. ASCO-GI 2013 #496). We analyzed subset of EGFR, K-ras, UGT1A1, and previous Bev. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2and bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. We retrospectively examined progression-free survival (PFS), overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety by K-ras, EGFR, UGT1A1, and previous Bev status. Results: Thirty-four patients were investigated. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 8.9 months, median TTF was 8.2 months and median OS was 23.4 months. Median PFS was 9.9 months on K-ras wild group and 6.6 months on K-ras mutant group (p = 0.517). Median OS was not reached on K-ras wild group and 16.4 months on K-ras mutant group (p = 0.097). The EGFR-negative case was three cases, and it did not become a data to compare because of small number. Median PFS was 8.5 months on previous Bev group and 9.9 months on previous no-Bev group (p = 0.637). Median OS was not reached on previous Bev group and 23.1 months on previous no-Bev group (p = 0.701). Median PFS, TTF and OS was no different between UGT1A1 wild group and mutant group. On safety analysis, there were no different between the two groups, respectively. Conclusions: IRIS/Bev is an active and well-tolerated second-line treatment for patients with mCRC. Only K-ras status influendced OS. Clinical trial information: UMIN000001631.

MAVERICC: A randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV with prospective biomarker stratification in previously untreated metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS3635-TPS3635 ◽  
Author(s):  
Sachdev P. Thomas ◽  
Suprith Badarinath ◽  
Richard H. Greenberg ◽  
Sang Y. Huh ◽  
Kulumani M Sivarajan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Predictive Biomarkers ◽  
Snp Markers ◽  
Open Label ◽  
Ecog Performance Status ◽  
The Impact

TPS3635^ Background: The identification of prognostic and predictive biomarkers could significantly improve the risk-benefit ratio and cost-effectiveness of 1st-line mCRC regimens. This is the first prospective study of tumoral ERCC1 (chemo-resistance marker to platinum compounds) and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively, in an effort to further define the optimal chemotherapy backbone with biologic therapies, including BV, for mCRC. Methods: In this randomized, open-label, global, phase II study, patients (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (high vs low, cutoff of 1.7 [ERCC1/β-actin mRNA]). Eligibility criteria include completion of adjuvant therapy >12 months before screening and an ECOG performance status ≤1. Blood samples are collected to quantify plasma VEGF-A levels. Patients within each ERCC1 stratification group are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. BV will be given at a dose of 5 mg/kg IV q2w. Patients will remain on study treatment until disease progression (PD) or unacceptable toxicity. If oxaliplatin or irinotecan need to be discontinued, BV and 5-fluorouracil or capecitabine are to be continued until PD. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing regimens in 1st-line mCRC, and 2) within ERCC1 high patients, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS compared to mFOLFOX6-BV. Secondary objectives include assessing the impact of these markers on overall survival, objective response, hepatic metastases resection, and safety. Exploratory endpoints include correlative analyses with additional tumor tissue, blood, and SNP markers. The first patient was enrolled in August 2011. An interim biomarker distribution assessment of the first 100 patients is planned, and the evaluation of the primary endpoints is estimated for early 2015. Clinicaltrials.gov: NCT01374425.

scholarly journals HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001279
Author(s):  
Yan Song ◽  
Ning Li ◽  
Qun Li ◽  
Xinjun Liang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Gastroesophageal Junction Cancer

BackgroundIrinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.MethodsThis multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.ResultsBetween October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.ConclusionThe combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.Trial registration numberNCT03704246

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4666-TPS4666
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Geert-Yan Creemers ◽  
Antonio Cubillo ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .

Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: Results from a multicenter, open-label, single-arm, phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16199-e16199
Author(s):  
Lin Shen ◽  
Xianjun Yu ◽  
Ming Lu ◽  
Xing Zhang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Neuroendocrine Carcinoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Grade 3

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

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]

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS783-TPS783
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Eric Van Cutsem ◽  
Jaime Feliu ◽  
Richard Greil ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS783 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment. Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC will be established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. Clinical trial information: NCT03665441.

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.

Trybeca-1: A randomized, phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS471-TPS471 ◽  
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Eric Van Cutsem ◽  
Jaime Feliu ◽  
Richard Greil ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3 ◽  
Eligibility Criteria

TPS471 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is an international, randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. An HR in OS of 0.725 is being targeted representing a conservative estimate based on the P2b data and is viewed as being highly clinically relevant. An IDMC will be established to review safety at regular intervals and to review efficacy data at the planned interim and final analyses. Clinical trial information: NCT03665441.

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