PARALLEL 303: Phase 2 randomized study of pamiparib vs placebo as maintenance therapy in patients (pts) with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line (1L) chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3109-3109
Author(s):  
Fortunato Ciardiello ◽  
Yung-Jue Bang ◽  
Johanna C. Bendell ◽  
Andres Cervantes ◽  
Mikhail Dvorkin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Maintenance Therapy ◽  
Primary Endpoint ◽  
Safety Profile ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Phase 2 ◽  
Platinum Based Chemotherapy ◽  
Grade 3

3109 Background: A subset of gastric cancers exhibits platinum sensitivity and genomic instability that is characteristic of homologous recombination deficiency (HRD). Cells with HRD are sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. PARP inhibitor maintenance therapy following platinum-based chemotherapy has been a successful treatment strategy in pts with ovarian cancer. Pamiparib is an orally administered selective PARP protein 1 and 2 (PARP1/2) inhibitor that has shown potent DNA-PARP trapping activity and crosses the blood brain barrier in preclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib showed an acceptable safety profile and promising antitumor activity. PARALLEL 303 compared the efficacy and safety of pamiparib vs placebo as maintenance therapy in pts with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based 1L chemotherapy. Methods: The primary endpoint of this double-blind, randomized, global phase 2 study (NCT03427814) was progression-free survival (PFS) as determined by the investigator per RECIST Version 1.1. Key secondary endpoints included time to subsequent treatment, objective response rate, duration of response, time to response, overall survival (OS) and safety. At the time of this analysis, OS data were immature due to the short duration of study. Data presented here will focus on PFS and safety. Results: 136 pts were randomized 1:1 to receive pamiparib 60 mg orally (PO) twice daily (BID) (n=71) or placebo PO BID (n=65) in 28-day cycles. The median PFS was longer with pamiparib vs placebo, but did not reach statistical significance (3.7 months; 95% CI, 1.94–5.26 vs 2.1 months; 95% CI, 1.87–3.75 months); hazard ratio 0.799 (95% CI, 0.534–1.193; P=0.1428). Treatment-emergent adverse events (TEAEs) of ≥ Grade 3 were experienced by 29 pts (40.8%) in the pamiparib arm, and 20 pts (30.8%) in the placebo arm. The most common TEAEs of ≥ Grade 3 were blood and lymphatic system disorders in the pamiparib arm, and gastrointestinal disorders in the placebo arm. TEAEs leading to treatment discontinuation were: 8 pts (11.3%) in the pamiparib arm and 2 pts (3.1%) in the placebo arm. TEAEs leading to death were: 2 pts (2.8%; 1 pneumonia, 1 unexplained) in the pamiparib arm, and 2 pts (3.1%; 1 hepatic rupture, 1 sepsis) in the placebo arm. Conclusions: Although pamiparib did not meet statistical significance for superiority vs placebo for its primary endpoint, it was generally well tolerated with few treatment discontinuations due to TEAEs. No new safety signals were identified with pamiparib, and its safety profile was consistent with that of other PARP inhibitors. Clinical trial information: NCT03427814.

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]

FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
Antoine Hollebecque ◽  
Juan W. Valle ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Disease Progression ◽  
Intrahepatic Cholangiocarcinoma ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Gene Fusions ◽  
Phase 2 ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy ◽  
Grade 3

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.

scholarly journals Three Weekly Irinotecan and Bolus 5-Fluorouracil Combination in the First Line Treatment of Advanced Gastric Cancer - A Single Institution Experience

2016 ◽  
Vol 3 (1) ◽  
pp. 19-22
Author(s):  
Mohamed Mesmoudi ◽  
Tarik Mahfoud ◽  
Samir Ahid ◽  
Nabil Ismaili ◽  
Saber Boutayeb ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Line Treatment ◽  
First Line ◽  
Infectious Episode ◽  
Locally Advanced Gastric Cancer ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
First Line Treatment

Background: The goal of this study is to determine the efficacy and toxicity of a non-platinum based chemotherapy combination using irinotecan associated to bolus 5-FU as first line treatment in advanced gastric cancer. Materiel and methods: Retrospective analysis of a population of patients treated for metastatic and locally advanced gastric cancer with irinotecan and 5-FU as upfront chemotherapy. Results: Thirteen patients were enrolled. The median age was 56 years. Seven patients were males and six were of females. Ten patients had a metastatic disease and three patients had a locally advanced disease. Patients received a total number of 43 cycles of chemotherapy. Overall response rate was 38,4%, median time to progression (TTP) was 3 months, and median overall survival was 4 months. Three patients (23,1%) presented grade 3 /4 neutropenia complicated with an infectious episode with fever in two cases, three patients (23,1%) required blood transfusion for a grade 4 anemia, and one patient (7,6%) was hospitalized for a severe episode of diarrhea. Conclusion: Three weekly irinotecan and bolus 5-FU is an interesting combination as first line treatment of advanced gastric cancer; designed clinical trials are needed to confirm the activity of this combination.

A Pilot Study of Irinotecan Combined with 5-Fluorouracil and Leucovorin for the Treatment of Chinese Patients with Locally Advanced and Metastatic Gastric Cancer

2009 ◽  
Vol 95 (4) ◽  
pp. 432-437 ◽  
Author(s):  
Qiu Li ◽  
Jing Chen ◽  
Xin Zhao ◽  
Xude Yin ◽  
Kai Mei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Partial Response ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Chinese Patients ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Comparative Trials

Aims and background The FOLFIRI regimen was evaluated for its anti-tumor activity and toxicity in Chinese patients with locally advanced and metastatic gastric cancer. Methods and study design Treatment consisted of irinotecan, 180 mg/m2 (90-min infusion), leucovorin, 200 mg/m2 (2-h infusion), followed by 5-fluorouracil, 400 mg/m2 (bolus), and then 5-fluorouracil, 600 mg/m2 (22-h continuous infusion) on days 1 and 2, every 14 days. Results Twenty-six patients, of whom 17 were pretreated, were included in the study. Partial response was observed in 9 patients (37.5%). The overall disease control rate was 83.3%. Median progression-free and overall survival was 6.8 and 11.2 months, respectively. Grade 3–4 neutropenia was observed in 6 patients (23.1%) and grade 2–3 diarrhea in 5 (19.2%). No treatment-related deaths occurred. Conclusions The results demonstrate that the FOLFIRI regimen is an active regimen with acceptable toxicity for Chinese patients with advanced and metastatic gastric cancer that merits further investigation in comparative trials.

A phase III, double-blind, randomized study of pamiparib versus placebo as maintenance therapy in patients with inoperable, locally advanced, or metastatic gastric cancer (GC) that responded to platinum-based first-line chemotherapy.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS173-TPS173 ◽  
Author(s):  
Fortunato Ciardiello ◽  
Yung-Jue Bang ◽  
Johanna C. Bendell ◽  
Andres Cervantes ◽  
Rainer Karl Brachmann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Maintenance Therapy ◽  
Randomized Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Platinum Based Chemotherapy

TPS173 Background: Gastric cancer is the fifth most common cancer, and is the third leading cause of cancer deaths worldwide. In patients with locally advanced or metastatic GC, fluoropyrimidine- and platinum-based combination chemotherapy is first-line standard of care. Despite refinement in chemotherapy regimens, outcomes are poor and survival after first-line treatment remains low. A subset of GCs exhibit platinum sensitivity and genomic instability that is characteristic of homologous recombination deficiency (HRD). Poly (ADP-ribose) polymerase proteins 1 and 2 (PARP1/2) are involved in DNA damage repair, and their inhibition is cytotoxic for cells with HRD. Pamiparib is a selective PARP1/2 inhibitor that crosses the blood-brain barrier, has shown potent DNA–PARP trapping, and has demonstrated antitumor activity in preclinical models. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib was generally well tolerated and showed preliminary antitumor activity; 60 mg oral twice daily (BID) was established as the recommended dose. Methods: This ongoing, global, double-blind, placebo-controlled, randomized, multicenter phase III study (NCT03427814) is designed to compare the efficacy, safety, and tolerability of pamiparib vs placebo as maintenance therapy in ~540 patients with advanced GC who have responded to first-line, platinum-based chemotherapy. Patients who are ≤ 8 weeks after their last dose of first-line platinum based chemotherapy will be randomized 1:1 to receive either pamiparib 60 mg BID or placebo in 28-day cycles. Patient randomization will be stratified by genomic loss of heterozygosity status (ie, high vs low), region, and ECOG status. Radiologic assessments will be centrally evaluated per RECIST every 8 weeks after first dose. The primary endpoint is progression-free survival; key secondary endpoints include safety/tolerability, overall survival, objective response rates, time and duration of response, and time to second subsequent treatment. Correlative biomarker analyses in tumor tissues and blood will be performed. Clinical trial information: NCT03427814.

scholarly journals Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 29 (1) ◽  
pp. 321-336
Author(s):  
Antonia Pagkali ◽  
Ioannis Mamais ◽  
Adamantios Michalinos ◽  
Aris P. Agouridis
Keyword(s):  
Ovarian Cancer ◽  
Adverse Effects ◽  
Maintenance Therapy ◽  
Safety Profile ◽  
Meta Analysis ◽  
Platinum Sensitive ◽  
Dichotomous Data ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Randomised Controlled

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

Oxaliplatin and irinotecan chemotherapy in advanced gastric cancer. Final results of a multicenter phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4070-4070 ◽  
Author(s):  
E. Woell ◽  
T. Kühr ◽  
W. Eisterer ◽  
K. Gattringer ◽  
R. Greil ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Treatment Options ◽  
Locally Advanced ◽  
Sensory Neuropathy ◽  
Metastatic Gastric Cancer ◽  
Female Ratio ◽  
Multiple Metastases ◽  
Grade 3 ◽  
Gastric Cancer Patients

4070 Background: There are only limited treatment options for advanced gastric cancer. Development of new treatment options is therefore warranted. The aim of this study was to evaluate the safety, feasibility and efficacy of an outpatient Oxaliplatin/Irinotecan combination in patients suffering from unresectable, locally advanced and/or metastatic gastric cancer. Methods: The combination of Oxaliplatin 85 mg/m2 biweekly with Irinotecan 125 mg/m2 biweekly was chosen since it has been shown in colorectal cancer that a biweekly dose of at least 85 mg/m2 oxaliplatin is superior to a lower dose and toxicity of Irinotecan is much lower if given fractionated into two doses. Furthermore the Irinotecan dose below MTD considers concerns about increased toxicity in gastric cancer patients. Results: 43 patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma and no previous palliative chemotherapy and/or immunotherapy were selected. Median age: 61 years (range 32–81 years), male/female ratio: 24/19, PS 0:11 patients, PS <3:32 patients, locally advanced cancer 5 patients, single metastatic site: 19 patients, multiple metastases: 19 patients, previously adjuvant radiochemotherapy: 4 patients. This outpatient regimen was generally well tolerated. Frequently reported adverse events (more than 20% of patients) were grade 1 or 2 and included neutropenia (44% of patients), thrombocytopenia (30%), anemia (77%), nausea 67%), diarrhea (51%), alopecia (35%). Grade 3 and 4 toxicities included neutropenia in 2/43 pts., anemia in 3/43 pts., nausea in 2/43 pts., and diarrhea in 4/43pts. 5 patients were taken off-study due to toxicity (asthenia, nausea, reversible renal failure, diarrhea). Sensory neuropathy occurred only as grade 2 in 14%, no grade 3/4 neurotoxicity was observed. For response 38 patients are assessable with 3 pts. (8%) showing a CR, PR in 19 pts. (50%), SD in 11 pts. (29%), PD in 5 pts. (13%). Median TTP was 5.3 months and median OS 9.5 months. Conclusions: The outpatient combination of a biweekly Oxaliplatin/Irinotecan chemotherapy is well tolerated and shows a response rate within the range of other combination therapies. The favourable toxicity profile makes it an alternative 1st line regimen. [Table: see text]

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